ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2021
Insulin signaling is an essential regulator of endometrial proliferation and implantation in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Validity of stem cell-loaded scaffolds to facilitate endometrial regeneration and restore fertility: a systematic review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- A transient epithelial plasticity state defines the developmental window for uterine gland specification.bioRxiv : the preprint server for biology · 2026Article
- Endometrial thickness evaluation with ultrasonography assessment among normal and endometrial cancer across multi-ethnic Indonesian women.Frontiers in reproductive health · 2026Article
- Conditional ablation of Insr and Igf1r using Esr2-Cre leads to abnormal ovarian follicle development and infertility in mice†.Biology of reproduction · 2025Article
- RHOX Homeobox Transcription Factor Regulation ofCells · 2025Article
- Uterine organoids reveal insights into epithelial specification and plasticity in development and disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Interplay of Uterine Health and Obesity: A Comprehensive Review.Biomedicines · 2024Review
- 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
- The updated understanding of advanced maternal age.Fundamental research · 2024Review
- The Roles of Obesity and ASB4 in Preeclampsia Pathogenesis.International journal of molecular sciences · 2024Review
- Trends of endometrial cancer incidence in Sri Lanka from 2011 to 2020: An analysis of annual national cancer incidence data reports.Journal of family medicine and primary care · 2024Article
- Article
- Unraveling the Dynamics of Estrogen and Progesterone Signaling in the Endometrium: An Overview.Cells · 2024Review
- Normal Ovarian Function in Subfertile Mouse withGenes · 2024Article
- Decreased NSD2 impairs stromal cell proliferation in human endometrium via reprogramming H3K36me2.Reproduction (Cambridge, England) · 2024Article
- Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis.BMC women's health · 2024Article
- Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.Journal of ovarian research · 2024Article
- Brain insulin action on peripheral insulin sensitivity in women depends on menstrual cycle phase.Nature metabolism · 2023Article
- Molecular Mechanisms of Endometriosis Revealed Using Omics Data.Biomedicines · 2023Review
- Dynamic peripheral blood microRNA expression landscape during the peri-implantation stage in women with successful pregnancy achieved by single frozen-thawed blastocyst transfer.Human reproduction open · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Insulin signaling is critical for the development of preovulatory follicles and progression through the antral stage. Using a conditional knockout model that escapes this blockage, we recently described the role of insulin signaling in granulosa cells during the periovulatory window in mice lacking Insr and Igf1r driven by Pgr-Cre. These mice were infertile, exhibiting defects in ovulation, luteinization, steroidogenesis, and early embryo development. Herein, we demonstrate that while these mice exhibit normal uterine receptivity, uterine cell proliferation and decidualization are compromised resulting in complete absence of embryo implantation in uteri lacking both receptors. While the histological organization of double knockout mice appeared normal, the thickness of their endometrium was significantly reduced. This was supported by the reduced proliferation of both epithelial and stromal cells during the preimplantation stages of pregnancy. Expression and localization of the main drivers of uterine proliferation, ESR1 and PGR, was normal in knockouts, suggesting that insulin signaling acts downstream of these two receptors. While AKT/PI3K signaling was unaffected by insulin receptor ablation, activation of p44/42 MAPK was significantly reduced in both single and double knockout uteri at 3.5 dpc. Overall, we conclude that both INSR and IGF1R are necessary for optimal endometrial proliferation and implantation.
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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.