ArticleProceedings of the National Academy of Sciences of the United States of America2016
Aberrant activation of canonical Notch1 signaling in the mouse uterus decreases progesterone receptor by hypermethylation and leads to infertility.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure.Human reproduction update · 2020Pooled it
- Decoding Müllerian Duct Epithelial Regionalization.Molecular reproduction and development · 2025Review
- The landscape ofBiomolecules & biomedicine · 2024Article
- The Known, the Unknown and the Future of the Pathophysiology of Endometriosis.International journal of molecular sciences · 2024Review
- Association betweenCurrent issues in molecular biology · 2024Article
- Effects of Ulipristal Acetate on Reactive Oxygen Species and Proinflammatory Cytokine Release by Epithelial and Stromal Cells from Human Endometrium and Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- In Silico Identification of a BRCA1:miR-29:DNMT3 Axis Involved in the Control of Hormone Receptors in BRCA1-Associated Breast Cancers.International journal of molecular sciences · 2023Article
- Endometrial stem/progenitor cells: Properties, origins, and functions.Genes & diseases · 2023Review
- Progesterone Resistance in Endometriosis: Current Evidence and Putative Mechanisms.International journal of molecular sciences · 2023Review
- Upregulation of FOXA2 in uterine luminal epithelium and vaginal basal epithelium of epiERα-/- (Esr1fl/flWnt7aCre/+) mice†.Biology of reproduction · 2023Article
- METTL3 is essential for normal progesterone signaling during embryo implantation via mProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.Frontiers in immunology · 2023Article
- Notch effector recombination signal binding protein for immunoglobulin kappa J signaling is required for the initiation of endometrial stromal cell decidualization†.Biology of reproduction · 2022Article
- Extracorporeal Shock Wave Therapy Combined with Platelet-Rich Plasma during Preventive and Therapeutic Stages of Intrauterine Adhesion in a Rat Model.Biomedicines · 2022Article
- Notch signaling in reproduction.Trends in endocrinology and metabolism: TEM · 2021Review
- Uterine Notch2 facilitates pregnancy recognition and corpus luteum maintenance via upregulating decidual Prl8a2.PLoS genetics · 2021Article
- Notch1 is crucial for decidualization and maintaining the first pregnancy in the mouse†.Biology of reproduction · 2021Article
- Article
- A fully-automated method discovers loss of mouse-lethal and human-monogenic disease genes in 58 mammals.Nucleic acids research · 2020Article
- Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity.Frontiers in cell and developmental biology · 2020Article
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Abstract
In mammalian reproduction, implantation is one of the most critical events. Failure of implantation and the subsequent decidualization contribute to more than 75% of pregnancy losses in women. Our laboratory has previously reported that inhibition of Notch signaling results in impaired decidualization in both women and a transgenic mouse model. In this study, we generated a Notch gain-of-function transgenic mouse by conditionally overexpressing the Notch1 intracellular domain (N1ICD) in the reproductive tract driven by a progesterone receptor (Pgr) -Cre. We show that the overexpression of N1ICD in the uterus results in complete infertility as a consequence of multiple developmental and physiological defects, including the absence of uterine glands and dysregulation of progesterone and estrogen signaling by a Recombination Signal Binding Protein Jκ-dependent signaling mechanism. We further show that the inhibition of progesterone signaling is caused by hypermethylation of its receptor Pgr by Notch1 overexpression through the transcription factor PU.1 and DNA methyltransferase 3b (Dnmt3b). We have generated a mouse model to study the consequence of increased Notch signaling in female reproduction and provide the first evidence, to our knowledge, that Notch signaling can regulate epigenetic modification of the Pgr.
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