All-trans-retinoic acid

evidence_span

{"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"}

experimental_model

Retinoid treatment and enzyme/mRNA measurements

exposure

All-trans, 13-cis and 9-cis retinoic acid exposure

limitations

Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human Y79 retinoblastoma-derived cells

plain_language

A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model.

primary_references

[melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x

tissue_or_cell_type

ASMT/HIOMT expression

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 292–303

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Retinoid treatment and enzyme/mRNA measurements · source_derived_draft · unverified_draft

### melatonin-retinoid-atra The tested retinoic-acid stereoisomer increased HIOMT mRNA and enzyme activity in Y79 cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin-A-derived signaling molecule can regulate this synthetic enzyme in a specific cell model. organism: Human Y79 retinoblastoma-derived cells tissue_or_cell_type: ASMT/HIOMT expression experimental_model: Retinoid treatment and enzyme/mRNA measurements limitations: Tumor-derived cell model. Retinoic acid is not synonymous with dietary vitamin A; no clinical vitamin A repletion or insomnia-treatment inference. exposure: All-trans, 13-cis and 9-cis retinoic acid exposure evidence_span: {"source_cache": "artifacts/melatonin-research/8752109.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b", "start_char": 0, "end_char": 650, "text_sha256": "d7a80b7b4106efe1c01849e3842ba968626d3a8c5401a5097b617da4d96ce83b"} [melatonin-p8752109] Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8752109/ DOI: 10.1046/j.1471-4159.1996.67031032.x

cross_nutrient

false

experimental_model

Paired cell-culture transcript assay

exposure

14-15 weeks gestation; 1 micromolar RA for 24 h; n=6.

limitations

A limited time and marker panel cannot prove permanent failure to enter meiosis.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

STRA8 induction did not activate the full tested meiotic marker panel.

primary_references

[human2011] Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. (2011). https://pubmed.ncbi.nlm.nih.gov/21674038/ DOI: 10.1371/journal.pone.0020249

tissue_or_cell_type

human fetal testis

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 343–354

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired cell-culture transcript assay · source_derived_draft · unverified_draft

### va-repro-human-meiotic-panel-boundary The same 24-hour RA exposure did not significantly increase SYCP3 or DMC1 RNA in human fetal testis cultures. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: STRA8 induction did not activate the full tested meiotic marker panel. organism: Homo sapiens tissue_or_cell_type: human fetal testis experimental_model: Paired cell-culture transcript assay limitations: A limited time and marker panel cannot prove permanent failure to enter meiosis. exposure: 14-15 weeks gestation; 1 micromolar RA for 24 h; n=6. cross_nutrient: false [human2011] Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. (2011). https://pubmed.ncbi.nlm.nih.gov/21674038/ DOI: 10.1371/journal.pone.0020249

cross_nutrient

false

experimental_model

Fetal ovarian organ culture

exposure

Meiotic entry examined in 10-11-week-post-fertilization ovaries; exact RA dose/time unavailable in abstract.

limitations

Ovaries at 8 weeks post fertilization or earlier did not enter meiosis simply with RA and serum.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

The human ovarian response depends on developmental readiness.

primary_references

[human2010] Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis. (2010). https://pubmed.ncbi.nlm.nih.gov/20670969/ DOI: 10.1093/humrep/deq195

tissue_or_cell_type

human fetal ovary

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 356–367

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Fetal ovarian organ culture · source_derived_draft · unverified_draft

### va-repro-human-ovary-ra-response RA increased meiotic cells in developmentally competent human fetal ovarian cultures. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human ovarian response depends on developmental readiness. organism: Homo sapiens tissue_or_cell_type: human fetal ovary experimental_model: Fetal ovarian organ culture limitations: Ovaries at 8 weeks post fertilization or earlier did not enter meiosis simply with RA and serum. exposure: Meiotic entry examined in 10-11-week-post-fertilization ovaries; exact RA dose/time unavailable in abstract. cross_nutrient: false [human2010] Meiosis initiation in the human ovary requires intrinsic retinoic acid synthesis. (2010). https://pubmed.ncbi.nlm.nih.gov/20670969/ DOI: 10.1093/humrep/deq195

cross_nutrient

false

experimental_model

Disaggregated fetal testis culture

exposure

14-15 weeks gestation; 1 micromolar RA for 24 h; n=5 for STRA8.

limitations

This transcript response does not establish entry into meiosis.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Human fetal testis cells can respond to RA by increasing STRA8.

primary_references

[human2011] Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. (2011). https://pubmed.ncbi.nlm.nih.gov/21674038/ DOI: 10.1371/journal.pone.0020249

tissue_or_cell_type

human fetal testis

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 330–341

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Disaggregated fetal testis culture · source_derived_draft · unverified_draft

### va-repro-human-stra8-induction RA increased STRA8 RNA 2.2-fold in cultured human fetal testis cells. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human fetal testis cells can respond to RA by increasing STRA8. organism: Homo sapiens tissue_or_cell_type: human fetal testis experimental_model: Disaggregated fetal testis culture limitations: This transcript response does not establish entry into meiosis. exposure: 14-15 weeks gestation; 1 micromolar RA for 24 h; n=5 for STRA8. cross_nutrient: false [human2011] Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad. (2011). https://pubmed.ncbi.nlm.nih.gov/21674038/ DOI: 10.1371/journal.pone.0020249

cross_nutrient

false

experimental_model

Mouse germ-cell expression analysis

exposure

RA-responsive expression; exact regimen unavailable in primary abstract.

limitations

Does not establish universal responsiveness at every spermatogonial stage.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

The vitamin A signal also induces a partner of STRA8.

primary_references

[ishiguro2020] MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. (2020). https://pubmed.ncbi.nlm.nih.gov/32032549/ DOI: 10.1016/j.devcel.2020.01.010

tissue_or_cell_type

developing germ cells

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 226–237

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse germ-cell expression analysis · source_derived_draft · unverified_draft

### va-repro-ra-meiosin-expression MEIOSIN expression responded to RA in the reported mouse germ-cell experiments. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: The vitamin A signal also induces a partner of STRA8. organism: Mus musculus tissue_or_cell_type: developing germ cells experimental_model: Mouse germ-cell expression analysis limitations: Does not establish universal responsiveness at every spermatogonial stage. exposure: RA-responsive expression; exact regimen unavailable in primary abstract. cross_nutrient: false [ishiguro2020] MEIOSIN Directs the Switch from Mitosis to Meiosis in Mammalian Germ Cells. (2020). https://pubmed.ncbi.nlm.nih.gov/32032549/ DOI: 10.1016/j.devcel.2020.01.010

cross_nutrient

false

experimental_model

Embryonic gonad culture

exposure

E12.5 testes; 0.7 micromolar RA for 2 days.

limitations

RNA induction alone did not establish completed meiosis.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

RA can turn on Stra8 in fetal testicular germ cells.

primary_references

[koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

tissue_or_cell_type

fetal testis

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 161–172

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryonic gonad culture · source_derived_draft · unverified_draft

### va-repro-ra-mouse-stra8 All-trans RA induced Stra8 RNA in cultured fetal mouse testes. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA can turn on Stra8 in fetal testicular germ cells. organism: Mus musculus tissue_or_cell_type: fetal testis experimental_model: Embryonic gonad culture limitations: RNA induction alone did not establish completed meiosis. exposure: E12.5 testes; 0.7 micromolar RA for 2 days. cross_nutrient: false [koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

duration

Culture treatment

experimental_model

Myeloid leukaemia cell lines and primary human AML models

exposure

All-trans retinoic acid

limitations

A transcript rise is not a measured rise in enzyme activity, and pharmacological ATRA is not dietary vitamin A.

organism

Homo sapiens

plain_language

Retinoic acid made leukaemia cells produce more of the TET2 enzyme.

primary_references

[celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

tissue

Myeloid leukaemia cells

TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 143–151

Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text. · supports · Myeloid leukaemia cell lines and primary human AML models · source_derived_draft · unverified_draft

## atra-induces-tet2-transcription All-trans retinoic acid induced retinoic-acid-receptor-alpha-mediated TET2 transcription in myeloid leukaemia cells. Model/species: Myeloid leukaemia cell lines and primary human AML models Organism: Homo sapiens Tissue/system: Myeloid leukaemia cells Exposure: All-trans retinoic acid Duration: Culture treatment Limits: A transcript rise is not a measured rise in enzyme activity, and pharmacological ATRA is not dietary vitamin A. Primary reference: [celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

duration

In vivo to survival

experimental_condition

Untreated or single-agent primary human AML models All-trans retinoic acid administered · All-trans-retinoic acid Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_condition

Untreated or single-agent primary human AML models Ascorbate administered · L-Ascorbate Condition belongs to the full experimental contrast; do not separate a joint intervention.

experimental_contrast

{"intervention": "All-trans retinoic acid plus ascorbate", "comparator": "Untreated or single-agent primary human AML models", "endpoint": "Leukaemia stem cell self-renewal and survival", "effect_direction": "decrease", "combination": "joint", "conditions": [{"entity_slug": "all-trans-retinoic-acid", "state": "All-trans retinoic acid administered"}, {"entity_slug": "ascorbate", "state": "Ascorbate administered"}]} Explicit extracted experimental comparison; source-derived draft.

experimental_model

Tet1/2/3-deficient mice and primary human AML models

exposure

All-trans retinoic acid combined with ascorbate

limitations

A joint intervention: the two agents were given together and this record cannot be read as the separate effect of either. TET2-dependence was shown with TET-deficient mice, which removes three paralogs rather than TET2 alone.

organism

Mus musculus and Homo sapiens

plain_language

Retinoic acid and vitamin C together worked better than either was expected to alone.

primary_references

[celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

tissue

Leukaemia stem cells

TET2 loss and malignancy: the step between a nutrient-responsive enzyme and the disease (2026-09-23) · lines 153–161

Original AI-assisted curation of twelve primary studies located by Europe PMC title search, with every statement drafted from the retrieved abstract. Two pairs share a laboratory and are recorded as one line of evidence each. Genetic loss of function, pharmacological exposure and dietary depletion are kept as separate record types. Not publisher full text. · supports · Tet1/2/3-deficient mice and primary human AML models · source_derived_draft · unverified_draft

## atra-with-ascorbate-reduces-lsc-self-renewal All-trans retinoic acid together with ascorbate induced differentiation and inhibited leukaemia stem cell self-renewal in a TET2-dependent manner in primary human acute-myeloid-leukaemia models, sensitised the cells to targeted therapies in vivo and improved survival. Model/species: Tet1/2/3-deficient mice and primary human AML models Organism: Mus musculus and Homo sapiens Tissue/system: Leukaemia stem cells Exposure: All-trans retinoic acid combined with ascorbate Duration: In vivo to survival Limits: A joint intervention: the two agents were given together and this record cannot be read as the separate effect of either. TET2-dependence was shown with TET-deficient mice, which removes three paralogs rather than TET2 alone. Primary reference: [celrep-2025] Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation (2025). https://pubmed.ncbi.nlm.nih.gov/41037397/ DOI: 10.1016/j.celrep.2025.116379

experimental_model

Cell-free assay and cell lines.

limitations

ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Different vitamin A forms were protective in the tested systems.

primary_references

[va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

tissue_or_cell_type

Cell-free chemistry and cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1789–1798

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free assay and cell lines. · source_derived_draft · unverified_draft

### va-atra-direct-radical-trapping2023 The 2023 study reported direct radical-trapping activity for retinol, retinal and ATRA alongside ferroptosis protection. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different vitamin A forms were protective in the tested systems. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry and cell cultures experimental_model: Cell-free assay and cell lines. limitations: ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference. [va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

cross_nutrient

Shared GPX4 connects retinoid signaling to the selenium collection; no proven supplementation synergy.

experimental_model

HT-1080 cells; pharmacological ATRA.

limitations

Direct promoter binding and dietary selenium replacement were not tested.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Retinoid signaling reached existing ferroptosis-defense machinery.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Human cell line

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1811–1821

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · HT-1080 cells; pharmacological ATRA. · source_derived_draft · unverified_draft

### va-atra-ferroptosis-regulators ATRA increased GPX4/FSP1 protein and GCH1 transcripts; RAR blockade suppressed the transcript responses. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Retinoid signaling reached existing ferroptosis-defense machinery. organism: Homo sapiens tissue_or_cell_type: Human cell line experimental_model: HT-1080 cells; pharmacological ATRA. limitations: Direct promoter binding and dietary selenium replacement were not tested. cross_nutrient: Shared GPX4 connects retinoid signaling to the selenium collection; no proven supplementation synergy. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

experimental_model

Human stem-cell neurons/organoids.

limitations

No dietary recommendation or evidence that vitamin A replaces vitamin E in humans.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Suppressing ferroptosis supported this developmental model.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Human neural cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1823–1832

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human stem-cell neurons/organoids. · source_derived_draft · unverified_draft

### va-atra-neuronal-ferroptosis-rescue ATRA or ferrostatin-1 rescued differentiation under antioxidant-deprived neuronal culture conditions. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suppressing ferroptosis supported this developmental model. organism: Homo sapiens tissue_or_cell_type: Human neural cultures experimental_model: Human stem-cell neurons/organoids. limitations: No dietary recommendation or evidence that vitamin A replaces vitamin E in humans. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

experimental_model

Cell-free assays.

limitations

Does not establish universal absence of antioxidant chemistry.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

Chemical form and assay conditions matter.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Cell-free chemistry

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1800–1809

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free assays. · source_derived_draft · unverified_draft

### va-atra-no-direct-radical-trapping2024 ATRA showed no direct activity in AAPH/C11-BODIPY and DPPH assays; retinol and retinal were active in the AAPH assay. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chemical form and assay conditions matter. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry experimental_model: Cell-free assays. limitations: Does not establish universal absence of antioxidant chemistry. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

cross_nutrient

Retinoid signaling -> calcium-store remodeling.

experimental_model

Neonatal mouse bone organ culture.

limitations

Receptor pharmacology is not proof of a human dietary effect.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

A vitamin A metabolite increased a signal that promotes bone resorption.

primary_references

[va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

tissue_or_cell_type

Calvarial bone

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1614–1624

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Neonatal mouse bone organ culture. · source_derived_draft · unverified_draft

### va-rar-alpha-rankl-bone Retinoic acid increased RANKL and the RANKL/OPG ratio in mouse calvarial cultures; receptor-selective results implicated RARalpha. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin A metabolite increased a signal that promotes bone resorption. organism: Mus musculus tissue_or_cell_type: Calvarial bone experimental_model: Neonatal mouse bone organ culture. limitations: Receptor pharmacology is not proof of a human dietary effect. cross_nutrient: Retinoid signaling -> calcium-store remodeling. [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

evidence_location

Abstract

experimental_model

Mouse diet/retinoic-acid interventions and human cell lines.

exposure

Retinoic-acid treatment with receptor-dependent tests.

limitations

Pharmacological treatment supports feedback circuitry, not a universal dietary threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus and Homo sapiens cell lines

outcome

Retinoic-acid receptor signaling increased intestinal ISX expression.

plain_language

The active retinoid metabolite induces a brake on further precursor uptake.

primary_references

[va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995

tissue_or_cell_type

Intestine and cultured cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 260–272

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse diet/retinoic-acid interventions and human cell lines. · source_derived_draft · unverified_draft

### va-retinoic-acid-isx-feedback Retinoic-acid receptor signaling increased intestinal ISX expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active retinoid metabolite induces a brake on further precursor uptake. organism: Mus musculus and Homo sapiens cell lines tissue_or_cell_type: Intestine and cultured cells experimental_model: Mouse diet/retinoic-acid interventions and human cell lines. limitations: Pharmacological treatment supports feedback circuitry, not a universal dietary threshold. exposure: Retinoic-acid treatment with receptor-dependent tests. outcome: Retinoic-acid receptor signaling increased intestinal ISX expression. evidence_location: Abstract [va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995

cross_nutrient

Retinoid signaling -> calcium/phosphate mineralization.

experimental_model

Primary human osteoblasts and MC3T3-E1 cells.

limitations

Pharmacology and culture exposure do not define a safe dietary threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens; Mus musculus

plain_language

Too much local retinoid signaling can impair mineral deposition in these models.

primary_references

[va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

tissue_or_cell_type

Osteoblasts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1650–1660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human osteoblasts and MC3T3-E1 cells. · source_derived_draft · unverified_draft

### va-retinoic-acid-mineralization Retinoic acid reduced mineralization in human and murine osteoblast models through RAR-linked effects. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Too much local retinoid signaling can impair mineral deposition in these models. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Osteoblasts experimental_model: Primary human osteoblasts and MC3T3-E1 cells. limitations: Pharmacology and culture exposure do not define a safe dietary threshold. cross_nutrient: Retinoid signaling -> calcium/phosphate mineralization. [va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

cross_nutrient

Vitamin A -> shared ALPL node already linked to zinc, magnesium and calcium.

experimental_model

Same culture experiments.

limitations

Parallel marker changes do not prove each mediates the mineralization loss.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens; Mus musculus

plain_language

Several components of the bone-building program changed together.

primary_references

[va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

tissue_or_cell_type

Osteoblasts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1662–1672

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same culture experiments. · source_derived_draft · unverified_draft

### va-retinoic-acid-osteoblast-markers RA-treated osteoblasts had reduced alkaline phosphatase and osteocalcin, with lower RUNX2/SP7 protein and PHEX expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several components of the bone-building program changed together. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Osteoblasts experimental_model: Same culture experiments. limitations: Parallel marker changes do not prove each mediates the mineralization loss. cross_nutrient: Vitamin A -> shared ALPL node already linked to zinc, magnesium and calcium. [va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

cross_nutrient

Retinoid/bone-cell stage-dependent response.

experimental_model

Human and mouse osteoclast progenitors.

limitations

Does not negate whole-bone resorption results; cell stage and neighboring cells differ.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens; Mus musculus

plain_language

The response differs when the experiment starts with isolated precursor cells.

primary_references

[va-hu2010] Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK (2010). https://pubmed.ncbi.nlm.nih.gov/20949013/ DOI: 10.1371/journal.pone.0013305

tissue_or_cell_type

Osteoclast precursors

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1638–1648

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse osteoclast progenitors. · source_derived_draft · unverified_draft

### va-retinoic-acid-precursor-rank Retinoic acid suppressed RANK and RANKL-driven osteoclast differentiation in progenitor cultures. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response differs when the experiment starts with isolated precursor cells. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Osteoclast precursors experimental_model: Human and mouse osteoclast progenitors. limitations: Does not negate whole-bone resorption results; cell stage and neighboring cells differ. cross_nutrient: Retinoid/bone-cell stage-dependent response. [va-hu2010] Retinoic acid increases proliferation of human osteoclast progenitors and inhibits RANKL-stimulated osteoclast differentiation by suppressing RANK (2010). https://pubmed.ncbi.nlm.nih.gov/20949013/ DOI: 10.1371/journal.pone.0013305

evidence_locator

Abstract

experimental_model

Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters.

exposure

Radioligand competition

limitations

Binding affinity is not a dietary threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors in African green monkey COS-1 cells

plain_language

The all-trans isomer directly engages RAR proteins.

primary_references

[va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

tissue_or_cell_type

Nuclear extracts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1030–1041

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. · source_derived_draft · unverified_draft

### va-sig-atra-rar-binding All-trans RA bound the tested RAR alpha, beta and gamma preparations with high affinity. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The all-trans isomer directly engages RAR proteins. organism: Recombinant receptors in African green monkey COS-1 cells tissue_or_cell_type: Nuclear extracts experimental_model: Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. limitations: Binding affinity is not a dietary threshold. evidence_locator: Abstract exposure: Radioligand competition [va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

evidence_locator

Abstract

experimental_model

Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters.

exposure

Isomer competition

limitations

Cell metabolism can alter apparent reporter responses.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors in COS-1 cells

plain_language

RAR and RXR cannot be treated as interchangeable RA receptors.

primary_references

[va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

tissue_or_cell_type

Nuclear extracts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1056–1067

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. · source_derived_draft · unverified_draft

### va-sig-atra-rxr-selectivity All-trans RA did not effectively compete for RXR binding in the tested isomer assay. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RAR and RXR cannot be treated as interchangeable RA receptors. organism: Recombinant receptors in COS-1 cells tissue_or_cell_type: Nuclear extracts experimental_model: Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. limitations: Cell metabolism can alter apparent reporter responses. evidence_locator: Abstract exposure: Isomer competition [va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

evidence_locator

Abstract

experimental_model

Genetically encoded FRET RA sensors in living zebrafish embryos.

exposure

Genetically encoded RA sensors

limitations

Sensor affinity, developmental stage and model constrain interpretation.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Danio rerio

plain_language

Embryonic cells encounter different local amounts of signaling RA.

primary_references

[va-shimozono-2013] Visualization of an endogenous retinoic acid gradient across embryonic development (2013). https://pubmed.ncbi.nlm.nih.gov/23563268/ DOI: 10.1038/nature12037

tissue_or_cell_type

Living early embryos

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1409–1420

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetically encoded FRET RA sensors in living zebrafish embryos. · source_derived_draft · unverified_draft

### va-sig-embryonic-ra-gradient FRET sensors visualized an endogenous RA concentration gradient during zebrafish gastrulation and somitogenesis. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Embryonic cells encounter different local amounts of signaling RA. organism: Danio rerio tissue_or_cell_type: Living early embryos experimental_model: Genetically encoded FRET RA sensors in living zebrafish embryos. limitations: Sensor affinity, developmental stage and model constrain interpretation. evidence_locator: Abstract exposure: Genetically encoded RA sensors [va-shimozono-2013] Visualization of an endogenous retinoic acid gradient across embryonic development (2013). https://pubmed.ncbi.nlm.nih.gov/23563268/ DOI: 10.1038/nature12037

evidence_locator

Abstract

experimental_model

RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy.

exposure

Experimental excess RA exposure

limitations

Not a quantitative human teratogenic threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Excess developmental signaling changed segment identity.

primary_references

[va-marshall-1992] Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity (1992). https://www.nature.com/articles/360737a0 DOI: 10.1038/360737a0

tissue_or_cell_type

Embryonic hindbrain

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1435–1446

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy. · source_derived_draft · unverified_draft

### va-sig-excess-ra-hindbrain-identity The exposed embryos showed rhombomere 2/3 transformation toward 4/5 identity with matching anatomical changes. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Excess developmental signaling changed segment identity. organism: Mus musculus tissue_or_cell_type: Embryonic hindbrain experimental_model: RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy. limitations: Not a quantitative human teratogenic threshold. evidence_locator: Abstract exposure: Experimental excess RA exposure [va-marshall-1992] Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity (1992). https://www.nature.com/articles/360737a0 DOI: 10.1038/360737a0

evidence_locator

Abstract

experimental_model

RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy.

exposure

Experimental excess RA exposure

limitations

Timing-specific teratogenic experiment, not ordinary dietary intake.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Excess RA can shift where an embryonic patterning gene is active.

primary_references

[va-marshall-1992] Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity (1992). https://www.nature.com/articles/360737a0 DOI: 10.1038/360737a0

tissue_or_cell_type

Preheadfold embryos/hindbrain

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1422–1433

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy. · source_derived_draft · unverified_draft

### va-sig-excess-ra-hox-pattern Preheadfold RA exposure altered segmental Hoxb1 reporter expression in mouse hindbrain. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Excess RA can shift where an embryonic patterning gene is active. organism: Mus musculus tissue_or_cell_type: Preheadfold embryos/hindbrain experimental_model: RA-exposed preheadfold transgenic mouse embryos; lacZ and anatomy. limitations: Timing-specific teratogenic experiment, not ordinary dietary intake. evidence_locator: Abstract exposure: Experimental excess RA exposure [va-marshall-1992] Retinoic acid alters hindbrain Hox code and induces transformation of rhombomeres 2/3 into a 4/5 identity (1992). https://www.nature.com/articles/360737a0 DOI: 10.1038/360737a0

evidence_locator

Abstract

experimental_model

Mouse Hoxb1 enhancer transgenes; homologous chicken and pufferfish elements.

exposure

Enhancer transgenes and RA exposure

limitations

Enhancer behavior is not a maternal serum-retinol threshold.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus; comparative chicken/pufferfish enhancer sequences

plain_language

Embryonic RA signaling connects to a spatial developmental gene program.

primary_references

[va-marshall-1994] A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1 (1994). https://www.nature.com/articles/370567a0 DOI: 10.1038/370567a0

tissue_or_cell_type

Early embryonic neuroectoderm

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1396–1407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse Hoxb1 enhancer transgenes; homologous chicken and pufferfish elements. · source_derived_draft · unverified_draft

### va-sig-hoxb1-ra-enhancer A conserved Hoxb1 enhancer containing a RARE mediated RA responsiveness and early neuroectodermal expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Embryonic RA signaling connects to a spatial developmental gene program. organism: Mus musculus; comparative chicken/pufferfish enhancer sequences tissue_or_cell_type: Early embryonic neuroectoderm experimental_model: Mouse Hoxb1 enhancer transgenes; homologous chicken and pufferfish elements. limitations: Enhancer behavior is not a maternal serum-retinol threshold. evidence_locator: Abstract exposure: Enhancer transgenes and RA exposure [va-marshall-1994] A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1 (1994). https://www.nature.com/articles/370567a0 DOI: 10.1038/370567a0

evidence_locator

Abstract

experimental_model

Biochemical interactions and engineered cellular transcription reporters.

exposure

Ligand addition

limitations

Cofactor exchange varies by promoter and cell.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Biochemical receptor system

plain_language

Ligand binding can release a transcriptional brake.

primary_references

[va-chen-1995] A transcriptional co-repressor that interacts with nuclear hormone receptors (1995). https://pubmed.ncbi.nlm.nih.gov/7566127/ DOI: 10.1038/377454a0

tissue_or_cell_type

Receptor complexes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1149–1160

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical interactions and engineered cellular transcription reporters. · source_derived_draft · unverified_draft

### va-sig-ligand-smrt-release Ligand destabilized SMRT association with retinoid receptor complexes, including DNA-bound receptors. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ligand binding can release a transcriptional brake. organism: Biochemical receptor system tissue_or_cell_type: Receptor complexes experimental_model: Biochemical interactions and engineered cellular transcription reporters. limitations: Cofactor exchange varies by promoter and cell. evidence_locator: Abstract exposure: Ligand addition [va-chen-1995] A transcriptional co-repressor that interacts with nuclear hormone receptors (1995). https://pubmed.ncbi.nlm.nih.gov/7566127/ DOI: 10.1038/377454a0

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_locator

Abstract

experimental_model

Human normal tracheobronchial epithelial air-liquid interface cultures.

exposure

RA withdrawal

limitations

Does not demonstrate airway infection protection.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

RA availability helps maintain the secretory phenotype in cultured airway cells.

primary_references

[va-yoon-1997] Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix (1997). https://pubmed.ncbi.nlm.nih.gov/9191474/ DOI: 10.1165/ajrcmb.16.6.9191474

tissue_or_cell_type

Normal tracheobronchial epithelial air-liquid interface culture

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1383–1394

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human normal tracheobronchial epithelial air-liquid interface cultures. · source_derived_draft · unverified_draft

### va-sig-ra-airway-secretion Removing RA from airway epithelial culture medium sharply reduced mucin secretion. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA availability helps maintain the secretory phenotype in cultured airway cells. organism: Homo sapiens tissue_or_cell_type: Normal tracheobronchial epithelial air-liquid interface culture experimental_model: Human normal tracheobronchial epithelial air-liquid interface cultures. limitations: Does not demonstrate airway infection protection. evidence_locator: Abstract exposure: RA withdrawal [va-yoon-1997] Regulation of the secretory phenotype of human airway epithelium by retinoic acid, triiodothyronine, and extracellular matrix (1997). https://pubmed.ncbi.nlm.nih.gov/9191474/ DOI: 10.1165/ajrcmb.16.6.9191474

evidence_locator

Abstract

experimental_model

Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice.

exposure

Added RA

limitations

Does not establish independent transcriptional induction of each subunit.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

RA helps activated T cells acquire an intestinal adhesion complex.

primary_references

[va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

tissue_or_cell_type

Activated T cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1188–1199

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. · source_derived_draft · unverified_draft

### va-sig-ra-alpha4beta7 RA during T-cell activation increased the alpha4beta7 gut-homing integrin. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA helps activated T cells acquire an intestinal adhesion complex. organism: Mus musculus tissue_or_cell_type: Activated T cells experimental_model: Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. limitations: Does not establish independent transcriptional induction of each subunit. evidence_locator: Abstract exposure: Added RA [va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

evidence_locator

Abstract

experimental_model

Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice.

exposure

Gut dendritic-cell-derived RA

limitations

Gut tropism alone is not IgA secretion.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

RA helps route antibody-producing cell precursors to the intestine.

primary_references

[va-mora-2006] Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells (2006). https://pubmed.ncbi.nlm.nih.gov/17110582/ DOI: 10.1126/science.1132742

tissue_or_cell_type

B-cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1214–1225

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice. · source_derived_draft · unverified_draft

### va-sig-ra-b-cell-homing Dendritic-cell-derived RA conferred gut tropism on activated B cells. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA helps route antibody-producing cell precursors to the intestine. organism: Mus musculus tissue_or_cell_type: B-cell cultures experimental_model: Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice. limitations: Gut tropism alone is not IgA secretion. evidence_locator: Abstract exposure: Gut dendritic-cell-derived RA [va-mora-2006] Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells (2006). https://pubmed.ncbi.nlm.nih.gov/17110582/ DOI: 10.1126/science.1132742

evidence_locator

Abstract

experimental_model

Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice.

exposure

Added RA

limitations

Receptor expression is distinct from clinical infection protection.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Activated cells acquire a receptor associated with gut entry.

primary_references

[va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

tissue_or_cell_type

Activated T cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1175–1186

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. · source_derived_draft · unverified_draft

### va-sig-ra-ccr9 RA during mouse T-cell activation increased CCR9 expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated cells acquire a receptor associated with gut entry. organism: Mus musculus tissue_or_cell_type: Activated T cells experimental_model: Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. limitations: Receptor expression is distinct from clinical infection protection. evidence_locator: Abstract exposure: Added RA [va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

evidence_locator

Abstract

experimental_model

Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice.

exposure

RA with IL-6 or IL-5

limitations

Cannot generalize to every IgA-switching pathway.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

IgA output required additional immune signals in this experiment.

primary_references

[va-mora-2006] Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells (2006). https://pubmed.ncbi.nlm.nih.gov/17110582/ DOI: 10.1126/science.1132742

tissue_or_cell_type

B-cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1227–1238

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice. · source_derived_draft · unverified_draft

### va-sig-ra-cytokine-iga RA alone was insufficient for IgA secretion but cooperated with IL-6 or IL-5 to induce it. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: IgA output required additional immune signals in this experiment. organism: Mus musculus tissue_or_cell_type: B-cell cultures experimental_model: Mouse B-cell/dendritic-cell systems and vitamin A-deficient mice. limitations: Cannot generalize to every IgA-switching pathway. evidence_locator: Abstract exposure: RA with IL-6 or IL-5 [va-mora-2006] Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells (2006). https://pubmed.ncbi.nlm.nih.gov/17110582/ DOI: 10.1126/science.1132742

evidence_locator

Abstract and Figure 3

experimental_model

Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models.

exposure

RA plus IL-15

limitations

No claim that dietary vitamin A causes coeliac disease.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

An inflammatory cytokine can redirect RA-associated immune signaling.

primary_references

[va-depaolo-2011] Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens (2011). https://www.nature.com/articles/nature09849 DOI: 10.1038/nature09849

tissue_or_cell_type

Dendritic cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1292–1303

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models. · source_derived_draft · unverified_draft

### va-sig-ra-il15-il12 RA with IL-15 promoted dendritic-cell IL-12p70 release. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inflammatory cytokine can redirect RA-associated immune signaling. organism: Mus musculus tissue_or_cell_type: Dendritic cells experimental_model: Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models. limitations: No claim that dietary vitamin A causes coeliac disease. evidence_locator: Abstract and Figure 3 exposure: RA plus IL-15 [va-depaolo-2011] Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens (2011). https://www.nature.com/articles/nature09849 DOI: 10.1038/nature09849

evidence_locator

Abstract and Figure 3

experimental_model

Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models.

exposure

RA plus IL-15

limitations

Different context from isolated naive T-cell induction.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

RA participates in a proinflammatory response in this cytokine setting.

primary_references

[va-depaolo-2011] Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens (2011). https://www.nature.com/articles/nature09849 DOI: 10.1038/nature09849

tissue_or_cell_type

Dendritic cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1305–1316

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models. · source_derived_draft · unverified_draft

### va-sig-ra-il15-il23 RA with IL-15 promoted dendritic-cell IL-23 release. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA participates in a proinflammatory response in this cytokine setting. organism: Mus musculus tissue_or_cell_type: Dendritic cells experimental_model: Mouse dendritic-cell/T-cell experiments and IL-15-rich intestinal models. limitations: Different context from isolated naive T-cell induction. evidence_locator: Abstract and Figure 3 exposure: RA plus IL-15 [va-depaolo-2011] Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens (2011). https://www.nature.com/articles/nature09849 DOI: 10.1038/nature09849

evidence_locator

Abstract

experimental_model

Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions.

exposure

Added RA in TGF-beta-driven differentiation

limitations

Not an unconditional anti-inflammatory effect or human dietary outcome.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

RA can cooperate with TGF-beta to favor regulatory cells.

primary_references

[va-mucida-2007] Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid (2007). https://pubmed.ncbi.nlm.nih.gov/17569825/ DOI: 10.1126/science.1145697

tissue_or_cell_type

Naive T-cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1253–1264

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions. · source_derived_draft · unverified_draft

### va-sig-ra-tgfb-foxp3 RA promoted regulatory T-cell differentiation under the tested TGF-beta-dependent conditions. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RA can cooperate with TGF-beta to favor regulatory cells. organism: Mus musculus tissue_or_cell_type: Naive T-cell cultures experimental_model: Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions. limitations: Not an unconditional anti-inflammatory effect or human dietary outcome. evidence_locator: Abstract exposure: Added RA in TGF-beta-driven differentiation [va-mucida-2007] Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid (2007). https://pubmed.ncbi.nlm.nih.gov/17569825/ DOI: 10.1126/science.1145697

evidence_locator

Abstract

experimental_model

Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions.

exposure

RA with IL-6/TGF-beta

limitations

New lineage induction differs from established intestinal Th17 effector function.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

The cytokine environment determines which T-cell differentiation program RA modifies.

primary_references

[va-mucida-2007] Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid (2007). https://pubmed.ncbi.nlm.nih.gov/17569825/ DOI: 10.1126/science.1145697

tissue_or_cell_type

Naive T-cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1266–1277

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions. · source_derived_draft · unverified_draft

### va-sig-ra-th17-differentiation Added RA inhibited IL-6-driven Th17 induction in the tested TGF-beta context. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytokine environment determines which T-cell differentiation program RA modifies. organism: Mus musculus tissue_or_cell_type: Naive T-cell cultures experimental_model: Mouse naive T-cell differentiation under TGF-beta and inflammatory cytokine conditions. limitations: New lineage induction differs from established intestinal Th17 effector function. evidence_locator: Abstract exposure: RA with IL-6/TGF-beta [va-mucida-2007] Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid (2007). https://pubmed.ncbi.nlm.nih.gov/17569825/ DOI: 10.1126/science.1145697

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 559–571

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a1-retinal-oxidation Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 573–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a2-retinal-oxidation Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 587–599

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a3-retinal-oxidation Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

evidence_access

Primary full text, Figure 2

experimental_model

Mouse immune-cell stimulation and Hcar2-deficient comparisons.

limitations

ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

A butyrate signal connected to vitamin A processing and immune regulation.

primary_references

Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 366–372

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse immune-cell stimulation and Hcar2-deficient comparisons. · source_derived_draft · unverified_draft

## butyrate-aldh1a1-immune A butyrate signal connected to vitamin A processing and immune regulation. Butyrate promoted Aldh1a1 and Il10 expression in mouse dendritic/macrophage experiments through Gpr109a signaling. Model: Mouse immune-cell stimulation and Hcar2-deficient comparisons. Limitations: ALDH expression does not by itself measure retinoic-acid flux or establish dietary vitamin A deficiency. Evidence access: Primary full text, Figure 2 Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text, Figure S2I and methods

experimental_model

Mouse dendritic/T-cell coculture; LE135 1 micromolar.

limitations

Antagonist exposure is not a vitamin A withdrawal experiment; extra vitamin A was not demonstrated to improve a replete response.

nutrient_topic

Butyrate collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Butyrate

plain_language

Blocking vitamin A–related receptor signaling removed this immune-cell response.

primary_references

Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007

trigger_kind

machinery_impairment Imported condition classification; unverified.

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 374–380

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse dendritic/T-cell coculture; LE135 1 micromolar. · source_derived_draft · unverified_draft

## butyrate-retinoid-block Blocking vitamin A–related receptor signaling removed this immune-cell response. The retinoic-acid-receptor antagonist LE135 abolished the increased Treg conversion induced by butyrate- or niacin-treated wild-type mouse dendritic cells. Model: Mouse dendritic/T-cell coculture; LE135 1 micromolar. Limitations: Antagonist exposure is not a vitamin A withdrawal experiment; extra vitamin A was not demonstrated to improve a replete response. Evidence access: Primary full text, Figure S2I and methods Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24412617/ · DOI 10.1016/j.immuni.2013.12.007

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Three conditional deletion strategies

exposure

Somatic or ubiquitous Aldh1a1-3 ablation; ovarian analyses around E13.5-E16.5.

limitations

Minor Stra8 delay occurred; analytically zero RA from every source was not demonstrated.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Removing the main RA-synthesis enzymes did not stop fetal ovarian meiosis.

primary_references

[chassot2020] Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary. (2020). https://pubmed.ncbi.nlm.nih.gov/32494737/ DOI: 10.1126/sciadv.aaz1261

tissue_or_cell_type

fetal ovary

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 291–302

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three conditional deletion strategies · source_derived_draft · unverified_draft

### va-repro-aldh-loss-ovarian-meiosis Conditional deletion of Aldh1a1, Aldh1a2 and Aldh1a3 did not prevent fetal ovarian meiotic progression despite strongly reduced RA. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the main RA-synthesis enzymes did not stop fetal ovarian meiosis. organism: Mus musculus tissue_or_cell_type: fetal ovary experimental_model: Three conditional deletion strategies limitations: Minor Stra8 delay occurred; analytically zero RA from every source was not demonstrated. exposure: Somatic or ubiquitous Aldh1a1-3 ablation; ovarian analyses around E13.5-E16.5. cross_nutrient: false [chassot2020] Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary. (2020). https://pubmed.ncbi.nlm.nih.gov/32494737/ DOI: 10.1126/sciadv.aaz1261

cross_nutrient

false

experimental_model

Embryonic gonad culture

exposure

E12.5 testes; 0.7 micromolar R115866 for 2 days.

limitations

The inhibitor experiment did not establish bona fide meiotic prophase.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Local retinoid breakdown restrains the Stra8 response.

primary_references

[koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

tissue_or_cell_type

fetal testis

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 174–185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryonic gonad culture · source_derived_draft · unverified_draft

### va-repro-cyp26-inhibitor-stra8 CYP26 inhibition with R115866 induced Stra8 in cultured fetal mouse testes. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Local retinoid breakdown restrains the Stra8 response. organism: Mus musculus tissue_or_cell_type: fetal testis experimental_model: Embryonic gonad culture limitations: The inhibitor experiment did not establish bona fide meiotic prophase. exposure: E12.5 testes; 0.7 micromolar R115866 for 2 days. cross_nutrient: false [koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Embryonic knockout comparison

exposure

Constitutive Cyp26b1 deletion; exact sampling ages unavailable in retrieved abstract.

limitations

This establishes a knockout phenotype, not a human RA dose threshold.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

A missing catabolic enzyme disrupts fetal male germ-cell timing.

primary_references

[bowles2006] Retinoid signaling determines germ cell fate in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16574820/ DOI: 10.1126/science.1125691

tissue_or_cell_type

fetal testis

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 200–211

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryonic knockout comparison · source_derived_draft · unverified_draft

### va-repro-cyp26b1-null-meiosis Cyp26b1-null mouse fetal testes contained germ cells entering meiosis precociously. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: A missing catabolic enzyme disrupts fetal male germ-cell timing. organism: Mus musculus tissue_or_cell_type: fetal testis experimental_model: Embryonic knockout comparison limitations: This establishes a knockout phenotype, not a human RA dose threshold. exposure: Constitutive Cyp26b1 deletion; exact sampling ages unavailable in retrieved abstract. cross_nutrient: false [bowles2006] Retinoid signaling determines germ cell fate in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16574820/ DOI: 10.1126/science.1125691

cross_nutrient

false

experimental_model

Pharmacologic model inference

exposure

E11.5 ovaries; 5 micromolar BMS-204493 for 2 days.

limitations

Disputed necessity inference; receptor repression differs from receptor deletion.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

An early drug experiment supported a requirement later challenged by genetics.

primary_references

[koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

tissue_or_cell_type

fetal ovary

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 187–198

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacologic model inference · source_derived_draft · unverified_draft

### va-repro-rar-necessity-model The 2006 study inferred that RAR signaling is required for fetal ovarian Stra8 induction after BMS-204493 suppressed its expression. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: An early drug experiment supported a requirement later challenged by genetics. organism: Mus musculus tissue_or_cell_type: fetal ovary experimental_model: Pharmacologic model inference limitations: Disputed necessity inference; receptor repression differs from receptor deletion. exposure: E11.5 ovaries; 5 micromolar BMS-204493 for 2 days. cross_nutrient: false [koubova2006] Retinoic acid regulates sex-specific timing of meiotic initiation in mice. (2006). https://pubmed.ncbi.nlm.nih.gov/16461896/ DOI: 10.1073/pnas.0510813103

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

CRISPR/Cas9 cis-regulatory mutation

exposure

RARE1 and RARE3 mutated singly or together; endogenous Stra8 expression assessed in vivo.

limitations

Reduced optimal expression does not establish complete loss of expression or prove an obligatory RA trigger for all ovarian meiosis.

nutrient_topic

Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Later genetic promoter tests confirmed a contribution from RA-responsive DNA elements.

primary_references

[feng2021] Identification of regulatory elements required for Stra8 expression in fetal ovarian germ cells of the mouse. (2021). https://pubmed.ncbi.nlm.nih.gov/33574039/ DOI: 10.1242/dev.194977

tissue_or_cell_type

fetal ovarian germ cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 395–406

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR/Cas9 cis-regulatory mutation · source_derived_draft · unverified_draft

### va-repro-stra8-rare-mutations Targeted mutation of Stra8 RA-response elements reduced its expression in fetal mouse ovaries. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Later genetic promoter tests confirmed a contribution from RA-responsive DNA elements. organism: Mus musculus tissue_or_cell_type: fetal ovarian germ cells experimental_model: CRISPR/Cas9 cis-regulatory mutation limitations: Reduced optimal expression does not establish complete loss of expression or prove an obligatory RA trigger for all ovarian meiosis. exposure: RARE1 and RARE3 mutated singly or together; endogenous Stra8 expression assessed in vivo. cross_nutrient: false [feng2021] Identification of regulatory elements required for Stra8 expression in fetal ovarian germ cells of the mouse. (2021). https://pubmed.ncbi.nlm.nih.gov/33574039/ DOI: 10.1242/dev.194977

cross_nutrient

true

evidence_location

Figure 3A–C

experimental_model

Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification

exposure

Retinol titration 0–50 ng/mL; 8-h and 72-h transcript assays.

limitations

Retinoid signaling and response depend on culture context; no claim that vitamin A supplementation demethylates adult human tissues.

nutrient_topic

Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C

organism

Mus musculus

plain_language

Vitamin A raised expression of DNA-modifying enzymes through a different route from vitamin C’s iron-redox effect.

primary_references

[c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

tissue_or_cell_type

Naïve embryonic stem cells

Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1047–1059

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification · source_derived_draft · unverified_draft

### c-reg-retinol-tet2-expression Retinol supplementation increased Tet2 transcription in mouse naïve ESCs within 8 h and after 72 h; Tet3 also responded, whereas evidence did not support direct retinol stimulation of TET catalytic efficiency. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A raised expression of DNA-modifying enzymes through a different route from vitamin C’s iron-redox effect. organism: Mus musculus tissue_or_cell_type: Naïve embryonic stem cells experimental_model: Mouse naïve ESCs in vitamin-A-free N2B27/2i medium; transcript quantification limitations: Retinoid signaling and response depend on culture context; no claim that vitamin A supplementation demethylates adult human tissues. exposure: Retinol titration 0–50 ng/mL; 8-h and 72-h transcript assays. cross_nutrient: true evidence_location: Figure 3A–C [c-reg-hore] Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. (2016). https://pubmed.ncbi.nlm.nih.gov/27729528/ DOI: 10.1073/pnas.1608679113

evidence_span

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experimental_model

Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification

exposure

Retinaldehyde with/without NAD+; selective inhibitors

limitations

Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Homo sapiens

plain_language

Different enzymes share vitamin A processing, and their contributions depend on the conditions.

primary_references

[mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

tissue_or_cell_type

Purified enzyme and liver S9 fractions

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 911–922

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification · source_derived_draft · unverified_draft

### mo-aox-aldh-partition In human liver S9, AOX inhibition reduced retinoic-acid formation by 20-50%, versus 50-80% with ALDH1A1 inhibition; AOX had lower affinity and higher capacity. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different enzymes share vitamin A processing, and their contributions depend on the conditions. organism: Homo sapiens tissue_or_cell_type: Purified enzyme and liver S9 fractions experimental_model: Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification limitations: Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage. exposure: Retinaldehyde with/without NAD+; selective inhibitors evidence_span: {"source_cache": "artifacts/molybdenum-research/33355213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2", "start_char": 0, "end_char": 2211, "text_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2"} [mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

evidence_span

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experimental_model

Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification

exposure

Retinaldehyde with/without NAD+; selective inhibitors

limitations

Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage.

nutrient_topic

Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum

organism

Homo sapiens

plain_language

A molybdenum enzyme can contribute to making vitamin A signaling molecules.

primary_references

[mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

tissue_or_cell_type

Purified enzyme and liver S9 fractions

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 898–909

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification · source_derived_draft · unverified_draft

### mo-aox-retinoic-acid Recombinant human AOX converted all-trans-retinaldehyde to all-trans-retinoic acid, with an apparent Km near 1.5 micromolar. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: A molybdenum enzyme can contribute to making vitamin A signaling molecules. organism: Homo sapiens tissue_or_cell_type: Purified enzyme and liver S9 fractions experimental_model: Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification limitations: Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage. exposure: Retinaldehyde with/without NAD+; selective inhibitors evidence_span: {"source_cache": "artifacts/molybdenum-research/33355213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2", "start_char": 0, "end_char": 2211, "text_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2"} [mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

cross_nutrient

NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested.

evidence_location

Abstract

experimental_model

Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.

exposure

All-trans-retinoic-acid concentration series with P450 reductase and NADPH.

limitations

Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens recombinant protein in insect cells

outcome

Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid.

plain_language

This P450 begins oxidative removal of the signaling retinoid.

primary_references

[va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

tissue_or_cell_type

Reconstituted enzyme/microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 601–614

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. · source_derived_draft · unverified_draft

### va-cyp26a1-primary-hydroxylation Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This P450 begins oxidative removal of the signaling retinoid. organism: Homo sapiens recombinant protein in insect cells tissue_or_cell_type: Reconstituted enzyme/microsomes experimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. limitations: Assay kinetics are not whole-body clearance; hydroxylated products are not assumed biologically inert. exposure: All-trans-retinoic-acid concentration series with P450 reductase and NADPH. outcome: Recombinant human CYP26A1 hydroxylated all-trans-retinoic acid to 4-hydroxy-retinoic acid. evidence_location: Abstract cross_nutrient: NADPH and heme-containing P450 machinery support retinoid oxidation; nutritional deficiency was not tested. [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

evidence_location

Abstract

experimental_model

Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays.

exposure

Substrate series with NADPH and P450 reductase.

limitations

Lower in vitro turnover than CYP26A1 does not mean lower importance in every tissue.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens recombinant protein in insect cells

outcome

Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid.

plain_language

A second independent P450 enzyme also removes the signaling precursor.

primary_references

[va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

tissue_or_cell_type

Reconstituted enzyme/microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 616–628

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. · source_derived_draft · unverified_draft

### va-cyp26b1-primary-hydroxylation Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second independent P450 enzyme also removes the signaling precursor. organism: Homo sapiens recombinant protein in insect cells tissue_or_cell_type: Reconstituted enzyme/microsomes experimental_model: Human CYP26A1/CYP26B1 expressed in insect cells; purified/reconstituted metabolism and tissue assays. limitations: Lower in vitro turnover than CYP26A1 does not mean lower importance in every tissue. exposure: Substrate series with NADPH and P450 reductase. outcome: Recombinant human CYP26B1 formed 4-hydroxy-retinoic acid from all-trans-retinoic acid. evidence_location: Abstract [va-topletz-2012] Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases (2012). https://pubmed.ncbi.nlm.nih.gov/22020119/ DOI: 10.1016/j.bcp.2011.10.007

cross_nutrient

Vitamin A/RANKL -> calcium release.

experimental_model

Same organ culture.

limitations

Preparation-specific causal intervention.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Blocking the RANKL signal interrupted the measured resorption response.

primary_references

[va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

tissue_or_cell_type

Bone

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1626–1636

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same organ culture. · source_derived_draft · unverified_draft

### va-opg-blocks-retinoid-calcium-release Exogenous OPG blocked retinoic-acid-stimulated labelled calcium release from calvarial bone. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking the RANKL signal interrupted the measured resorption response. organism: Mus musculus tissue_or_cell_type: Bone experimental_model: Same organ culture. limitations: Preparation-specific causal intervention. cross_nutrient: Vitamin A/RANKL -> calcium release. [va-conaway2011] Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor (2011). https://pubmed.ncbi.nlm.nih.gov/21715325/ DOI: 10.1074/jbc.m111.247734

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing.

limitations

Residual activity and other enzymes prevent an exclusive RDH10 interpretation.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

outcome

Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells.

plain_language

Reducing precursor oxidation lowered downstream active retinoid production.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 502–514

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-silencing-ra Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing precursor oxidation lowered downstream active retinoid production. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Residual activity and other enzymes prevent an exclusive RDH10 interpretation. exposure: RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing. outcome: Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. evidence_location: Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_locator

Abstract

experimental_model

Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice.

exposure

Vitamin A-deficient diet

limitations

Does not isolate trafficking from all other deficiency effects.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Mus musculus

plain_language

Dietary depletion changed the intestinal T-cell compartment.

primary_references

[va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

tissue_or_cell_type

Intestinal lamina propria

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1201–1212

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. · source_derived_draft · unverified_draft

### va-sig-deficient-intestinal-t-cells Vitamin A-deficient mice had depleted intestinal lamina propria T cells. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Dietary depletion changed the intestinal T-cell compartment. organism: Mus musculus tissue_or_cell_type: Intestinal lamina propria experimental_model: Mouse activated T cells, gut dendritic cells and vitamin A-deficient mice. limitations: Does not isolate trafficking from all other deficiency effects. evidence_locator: Abstract exposure: Vitamin A-deficient diet [va-iwata-2004] Retinoic acid imprints gut-homing specificity on T cells (2004). https://pubmed.ncbi.nlm.nih.gov/15485630/ DOI: 10.1016/j.immuni.2004.08.011

evidence_locator

Abstract

experimental_model

Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists.

exposure

Receptor-selective agonists/antagonists

limitations

Transcript changes do not establish improved mucus clearance.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Homo sapiens

plain_language

RAR signaling helps cultured airway cells adopt a mucus-producing program.

primary_references

[va-koo-1999] Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells (1999). https://pubmed.ncbi.nlm.nih.gov/10024510/ DOI: 10.1042/bj3380351

tissue_or_cell_type

Normal tracheobronchial epithelial cells

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1357–1368

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists. · source_derived_draft · unverified_draft

### va-sig-rara-airway-mucin RAR alpha-selective pharmacology supported RAR alpha-mediated induction of airway mucin transcripts, including MUC5AC. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RAR signaling helps cultured airway cells adopt a mucus-producing program. organism: Homo sapiens tissue_or_cell_type: Normal tracheobronchial epithelial cells experimental_model: Normal human tracheobronchial epithelial cultures with receptor-selective agonists/antagonists. limitations: Transcript changes do not establish improved mucus clearance. evidence_locator: Abstract exposure: Receptor-selective agonists/antagonists [va-koo-1999] Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells (1999). https://pubmed.ncbi.nlm.nih.gov/10024510/ DOI: 10.1042/bj3380351

evidence_locator

Abstract

experimental_model

Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters.

exposure

Agonist versus control; AF-2 mutants

limitations

Domain assays do not resolve every endogenous chromatin complex.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Human TIF2 and engineered receptor domains

plain_language

An activated receptor gains a binding surface for a transcriptional coactivator.

primary_references

[va-voegel-1996] TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors (1996). https://pubmed.ncbi.nlm.nih.gov/8670870/ DOI: 10.1002/j.1460-2075.1996.tb00736.x

tissue_or_cell_type

Cell-free and cellular interaction assays

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1162–1173

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters. · source_derived_draft · unverified_draft

### va-sig-rara-tif2-recruitment The agonist-bound RAR ligand-binding domain interacted with TIF2 in an AF-2-dependent manner. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: An activated receptor gains a binding surface for a transcriptional coactivator. organism: Human TIF2 and engineered receptor domains tissue_or_cell_type: Cell-free and cellular interaction assays experimental_model: Human TIF2 cloning; in vitro receptor-domain interactions and cellular reporters. limitations: Domain assays do not resolve every endogenous chromatin complex. evidence_locator: Abstract exposure: Agonist versus control; AF-2 mutants [va-voegel-1996] TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors (1996). https://pubmed.ncbi.nlm.nih.gov/8670870/ DOI: 10.1002/j.1460-2075.1996.tb00736.x

evidence_locator

Abstract

experimental_model

Receptor interaction, DNA binding and transfection experiments.

exposure

Receptor cotransfection and RA

limitations

Reporter-system dependence; no nutrient dose response.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Engineered cellular receptor system

plain_language

RXRA can assist RAR signaling without equivalent activation of both partners.

primary_references

[va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0

tissue_or_cell_type

Transfection reporters

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1123–1134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor interaction, DNA binding and transfection experiments. · source_derived_draft · unverified_draft

### va-sig-rxra-rar-transactivation RXRA enhanced RAR-mediated transcription at RA concentrations insufficient to substantially activate RXRA itself. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RXRA can assist RAR signaling without equivalent activation of both partners. organism: Engineered cellular receptor system tissue_or_cell_type: Transfection reporters experimental_model: Receptor interaction, DNA binding and transfection experiments. limitations: Reporter-system dependence; no nutrient dose response. evidence_locator: Abstract exposure: Receptor cotransfection and RA [va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0