ArticleReproductive biology and endocrinology : RB&E2023
METTL3-regulated m6A modification impairs the decidualization of endometrial stromal cells by regulating YTHDF2-mediated degradation of FOXO1 mRNA in endometriosis-related infertility.
Article in Reproductive biology and endocrinology : RB&E, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- GnRH Promotes Gonadotropin Synthesis and Secretion in the Bovine Anterior Pituitary by Inhibiting METTL1-Mediated m7G Modification of FOXO1 mRNA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- ALKBH5 Positively Regulates BMP2 to Influence Endometrial Decidualization in Recurrent Spontaneous Abortion.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The role of the SIRT1/FOXO1 axis in regulating autophagy and inflammation in endometriosis.Journal of translational medicine · 2026Article
- FTO Controls Endometrial Receptivity and Embryo Implantation through Regulating mCommunications biology · 2026Article
- Unravelling Multilayered RNA Modification Networks in Female Reproduction and Obstetric/Gynaecologic Disorders.Biomolecules · 2026Review
- Epitranscriptomics as a Candidate Universal Modulator of Dormancy Transitions.Ecology and evolution · 2026Review
- The role of mGenes & diseases · 2026Review
- YTHDF2 enhances proliferation and metastasis of nasopharyngeal carcinoma by mediating m6A modification in destabilizing FOXO1 mRNA.Cancer biology & therapy · 2025Article
- PRMT3-mediated FOXO1 arginine methylation exacerbates oxidative stress-induced decidualization defects in the eutopic endometrium of endometriosis.Cellular and molecular life sciences : CMLS · 2025Article
- Molecular Regulation of FOXO1 and Its Pathophysiological Significance in Endometriosis: A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Identified endoplasmic reticulum stress-related molecular cluster and immune characterization in endometriosis.Scientific reports · 2025Article
- Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology.International journal of molecular sciences · 2025Review
- Review
- Remimazolam alleviates hepatic ischemia-reperfusion injury by activating FOXO1/3 signaling : Remimazolam alleviates hepatic ischemia reperfusion injury.BMC gastroenterology · 2025Article
- Exploring the role and therapeutic potential of RNA N6-methyladenosine modification in abortion disease pathology: a comprehensive review.Frontiers in genetics · 2025Review
- Identification and Characterization of m6A Regulators METTL3 and YTHDF2: Unveiling Their Biological Functions in Endometriosis.International journal of women's health · 2025Article
- Update on the pathogenesis of endometriosis-related infertility based on contemporary evidence.Frontiers in endocrinology · 2025Review
- Regulated Cell Death in Endometriosis.Biomolecules · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundEndometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation.
methodsWe examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A.
resultsThe expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein.
conclusionsMETTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
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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 Socratic graph.