ArticleJCI insight2021
Signaling through retinoic acid receptors is essential for mammalian uterine receptivity and decidualization.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Nutritional Regulation of Reproductive Physiology in Ruminants: A Mechanistic Review.Life (Basel, Switzerland) · 2026Review
- Nutritional regulation of sow reproduction by vitamin A: insights and knowledge gaps.Porcine health management · 2026Review
- Digestibility and transcriptomic profiling of kidney, pancreas, follicle, and uterus in laying hens supplemented with phytogenic feed additive.Poultry science · 2026Article
- SALL1 Is an Orchestrator of Uterine Receptivity in Part via Titration of Estrogen Signaling.Endocrinology · 2025Article
- Fibroblast growth factors and endometrial decidualization: models, mechanisms, and related pathologies.Journal of Zhejiang University. Science. B · 2025Review
- Retinoic acid antagonizes estrogen signaling to maintain adult uterine cell fate.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoding Müllerian Duct Epithelial Regionalization.Molecular reproduction and development · 2025Review
- Signaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Assessment of reproductive challenges and nutritional practices on Pennsylvania sow farms.Translational animal science · 2025Article
- Cellular heterogeneity and dynamics of the human uterus in healthy premenopausal women.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Pet Wellness and Vitamin A: A Narrative Overview.Animals : an open access journal from MDPI · 2024Review
- Attenuated retinoic acid signaling is among the early responses in mouse uterus approaching embryo attachment.Reproductive and developmental medicine · 2024Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Communications biology · 2024Article
- Streamlined identification of clinically and functionally relevant genetic regulators of lower-tract urogenital development.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mapping Expression Quantitative Trait Loci Targeting Candidate Genes for Pregnancy in Beef Cows.Biomolecules · 2024Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Research square · 2023Article
- Stromal cells-specific retinoic acid determines parturition timing at single-cell and spatial-temporal resolution.iScience · 2023Article
- Role of EZH2 in Uterine Gland Development.International journal of molecular sciences · 2022Article
- Deficiency of RARα Suppresses DecidualizationFrontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. Reduction in RA signaling activity severely affects the ability of the uterus to achieve receptive status and decidualize, partially through dampening follistatin expression and downstream activin B/bone morphogenetic protein 2 signaling. To confirm translational relevance of these findings to humans, human endometrial stromal cells (hESCs) were treated with a pan-RAR antagonist to show that in vitro decidualization is impaired. RNA interference perturbation of individual RAR transcripts in hESCs revealed that RARα in particular was essential for proper decidualization. These data provide direct functional evidence that uterine RAR-mediated RA signaling was crucial for mammalian embryo implantation, and its disruption led to failure of uterine receptivity and decidualization, resulting in severely compromised fertility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.