ArticleDevelopmental biology2017
Retinoic acid signaling is dispensable for somatic development and function in the mammalian ovary.
Article in Developmental biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- A systematic review of retinoic acid in the journey of spermatogonium to spermatozoa: From basic to clinical application.F1000Research · 2022Pooled it
- Retinoic acid disrupts cumulus granulosa cells function via EGFR downregulation: induction of PCOS and infertility in adult female mice.Histochemistry and cell biology · 2026Article
- Porcine granulosa cell transcriptomic analyses reveal the differential regulation of lncRNAs and mRNAs in response to all-trans retinoic acid in vitro.Animal bioscience · 2025Article
- AOP Report: Decreased ALDH1A (RALDH) activity leading to decreased fertility via disrupted meiotic initiation of fetal oogonia.Current research in toxicology · 2025Article
- The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes.The Journal of experimental medicine · 2024Review
- Retinoic acid enhances ovarian steroidogenesis by regulating granulosa cell proliferation and MESP2/STAR/CYP11A1 pathway.Journal of advanced research · 2024Article
- Identification and Expression Pattern ofAnimals : an open access journal from MDPI · 2022Article
- Retinoic acid can improve autophagy through depression of the PI3K-Akt-mTOR signaling pathway via RARα to restore spermatogenesis in cryptorchid infertile rats.Genes & diseases · 2022Article
- Developmental dynamics of sex reprogramming by high incubation temperatures in a dragon lizard.BMC genomics · 2022Article
- Dissecting Human Gonadal Cell Lineage Specification and Sex Determination Using A Single-cell RNA-seq Approach.Genomics, proteomics & bioinformatics · 2022Article
- AOP Key Event Relationship report: Linking decreased retinoic acid levels with disrupted meiosis in developing oocytes.Current research in toxicology · 2022Article
- Nuclear Receptors in Ovarian Function.Advances in experimental medicine and biology · 2022Article
- The cell surface hyaluronidase TMEM2 is essential for systemic hyaluronan catabolism and turnover.The Journal of biological chemistry · 2021Article
- Signaling through retinoic acid receptors is essential for mammalian uterine receptivity and decidualization.JCI insight · 2021Article
- A transitory signaling center controls timing of primordial germ cell differentiation.Developmental cell · 2021Article
- Diabetogenic diet-induced insulin resistance associates with lipid droplet proteins and adipose tissue secretome, but not with sexual dimorphic adipose tissue fat accumulation in wistar rats.Biochemistry and biophysics reports · 2020Article
- Reduced retinoic acid synthesis accelerates prophase I and follicle activation.Reproduction (Cambridge, England) · 2020Article
- Retinoic acid synthesis by ALDH1A proteins is dispensable for meiosis initiation in the mouse fetal ovary.Science advances · 2020Article
- Retinoic acid signaling in ovarian folliculogenesis and steroidogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2019Review
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Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Retinoic acid (RA) is a potent inducer of cell differentiation and plays an essential role in sex-specific germ cell development in the mammalian gonad. RA is essential for male gametogenesis and hence fertility. However, RA can also disrupt sexual cell fate in somatic cells of the testis, promoting transdifferentiation of male Sertoli cells to female granulosa-like cells when the male sexual regulator Dmrt1 is absent. The feminizing ability of RA in the Dmrt1 mutant somatic testis suggests that RA might normally play a role in somatic cell differentiation or cell fate maintenance in the ovary. To test for this possibility we disrupted RA signaling in somatic cells of the early fetal ovary using three genetic strategies and one pharmaceutical approach. We found that deleting all three RA receptors (RARs) in the XX somatic gonad at the time of sex determination did not significantly affect ovarian differentiation, follicle development, or female fertility. Transcriptome analysis of adult triple mutant ovaries revealed remarkably little effect on gene expression in the absence of somatic RAR function. Likewise, deletion of three RA synthesis enzymes (Aldh1a1-3) at the time of sex determination did not masculinize the ovary. A dominant-negative RAR transgene altered granulosa cell proliferation, likely due to interference with a non-RA signaling pathway, but did not prevent granulosa cell specification and oogenesis or abolish fertility. Finally, culture of fetal XX gonads with an RAR antagonist blocked germ cell meiotic initiation but did not disrupt sex-biased gene expression. We conclude that RA signaling, although crucial in the ovary for meiotic initiation, is not required for granulosa cell specification, differentiation, or reproductive function.
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Registered trials
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