ArticlePloS one2017
Reprogramming of the retinoic acid pathway in decidualizing human endometrial stromal cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Trial
- Novel Models to Predict Pregnancy for Patients Receiving In-Vitro-Fertilization Embryo Transfer: The Significance of Clinical Indicators and Key Gene Expression in the Endometrium.Biochemical genetics · 2026Article
- 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
- Metabolic reprogramming and heterogeneity during the decidualization process of endometrial stromal cells.Cell communication and signaling : CCS · 2024Article
- Effects of conceptus proteins on endometrium and blood leukocytes of dairy cattle using transcriptome and meta-analysis.bioRxiv : the preprint server for biology · 2024Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Communications biology · 2024Article
- Impaired bone morphogenetic protein (BMP) signaling pathways disrupt decidualization in endometriosis.Research square · 2023Article
- Proteomic Analysis of Endometrial Cancer Tissues from Patients with Type 2 Diabetes Mellitus.Life (Basel, Switzerland) · 2022Article
- Deficiency of RARα Suppresses DecidualizationFrontiers in endocrinology · 2022Article
- Signaling through retinoic acid receptors is essential for mammalian uterine receptivity and decidualization.JCI insight · 2021Article
- Modelling the impact of decidual senescence on embryo implantation in human endometrial assembloids.eLife · 2021Article
- Identification and Characterization of lncRNA and mRNA in Testes of Landrace and Hezuo Boars.Animals : an open access journal from MDPI · 2021Article
- Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Trophoblast Functions.International journal of molecular sciences · 2021Review
- Human Endometrial Stromal Cell Differentiation is Stimulated by PPARβ/δ Activation: New Targets for Infertility?The Journal of clinical endocrinology and metabolism · 2020Article
- Aberrant retinoic acid production in the decidua: Implications for pre-eclampsia.The journal of obstetrics and gynaecology research · 2020Review
- Contribution of senescence in human endometrial stromal cells during proliferative phase to embryo receptivity†.Biology of reproduction · 2020Article
- Endometrial Decidualization: The Primary Driver of Pregnancy Health.International journal of molecular sciences · 2020Review
- Preconception resveratrol intake against infertility: Friend or foe?Reproductive medicine and biology · 2020Review
- Alternatively Activated Macrophages Are the Primary Retinoic Acid-Producing Cells in Human Decidua.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Retinoic Acid Is a Negative Regulator of sFLT1 Expression in Decidual Stromal Cells, and Its Levels Are Reduced in Preeclamptic Decidua.Hypertension (Dallas, Tex. : 1979) · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon breaching of the endometrial surface epithelium, the implanting embryo embeds in the decidualizing stroma. Retinoic acid (RA), a metabolite of vitamin A, is an important morphogen during embryonic and fetal development, although the role of the RA pathway in the surrounding decidual cells is not understood. Here we show that decidual transformation of human endometrial stromal cells (HESCs) results in profound reprogramming of the RA signaling and metabolism pathways. Differentiating HESCs downregulate the intracellular carrier proteins CRABP2 and FABP5, responsible for transfer and binding of RA to the nuclear receptors RAR and PPARβ/δ, respectively. Furthermore, the expression of RAR, the receptor that mediates the pro-apoptotic effects of RA, was also inhibited. By contrast, PPARβ/δ, which transduces the differentiation responses of RA, was upregulated. Decidualization was also associated with increased expression of retinol-binding protein 4 (RBP4) and various enzymes involved in the metabolism of RA and its precursor, retinaldehyde (Rald), including CYP26A1, DHRS3, and RDH12. Exposure of differentiating HESCs to RA or Rald reversed the inhibition of the CRABP2-RAR pathway, perturbed the expression of decidual marker genes and triggered cell death. Taken together, the data demonstrate that decidualizing HESCs silence RA signaling by downregulating key cytoplasmic binding proteins and by increasing retinoid metabolism. However, excessive RA exposure is toxic for decidual cells and triggers a response that may lead to pregnancy failure.
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Registered trials
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