ArticleJournal of ovarian research2024
Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.
Article in Journal of ovarian research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 12 citations in OpenAlex.
- NR4A1-Driven Granulosa Cell Ferroptosis Contributes to Obesity-Related Ovarian Dysfunction and Metformin-Mediated Ovarian Protection.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A Biological Disease-Staging Model of Polyendocrine Metabolic Ovarian Syndrome: From Plasticity-Dominant States to Pathological Remodeling.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Advances in the Study of Endometrial Receptivity and Glucose Metabolism Mechanisms in Insulin Resistance.Endocrinology, diabetes & metabolism · 2026Review
- Molecular Mechanisms Underlying Reproductive Dysfunction in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- A Review of the Potential Therapeutic Benefits of Quercetin for Uterine-Related Conditions.Biomedicines · 2026Review
- A Comprehensive Review on Recent Advancements in Navigating the Complexities of Polycystic Ovarian Syndrome (PCOS).Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Mechanisms and clinical implications of oxidative stress-mediated endometrial receptivity impairment in polycystic ovary syndrome.Journal of ovarian research · 2026Review
- Elevated plasma glucose links intrafollicular bile acids to altered embryological outcomes in IVF patients.Journal of ovarian research · 2025Article
- Molecular Impact of Metabolic and Endocrine Disturbance on Endometrial Function in Polycystic Ovary Syndrome.International journal of molecular sciences · 2025Review
- Unraveling the multifactorial pathophysiology of polycystic ovary syndrome: exploring lifestyle, prenatal influences, neuroendocrine dysfunction, and post-translational modifications.Molecular biology reports · 2025Review
- Semaglutide ameliorates cardiac remodeling in male mice by optimizing energy substrate utilization through the Creb5/NR4a1 axis.Nature communications · 2024Article
- Incretin Hormone Secretion in Women with Polycystic Ovary Syndrome: Roles of Obesity, Insulin Sensitivity and Treatment with Metformin and GLP-1s.Biomedicines · 2024Review
- Association of body roundness index with female infertility: 2013-2018 NHANES.Frontiers in nutrition · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInvestigating the underlying molecular mechanisms responsible for endometrial dysfunction in women with PCOS is essential, particularly focusing on the role of hyperinsulinemia.
methodsWe explored the role of insulin in the decidualization process using a synthetic decidualization assay. To dissect the effects of PI3K/AKT-NR4A signaling, we employed small interfering RNAs (siRNAs) targeting the NR4A genes and inhibitors of the PI3K/AKT pathway. We also investigated the disruption of AKT-NR4A1 signaling in the endometrium of PCOS female rats induced with dehydroepiandrosterone (DHEA). Quantitative real-time PCR (qRT-PCR) and Western blot (WB) analyses were utilized to evaluate gene expression regulation.
resultsInsulin was found to suppress the expression of decidualization markers in human endometrial stromal cells (hESC) in a dose-dependent manner, concurrently triggering an inappropriate activation of the PI3K/AKT pathway. Members of the NR4A family, as downstream effectors in the PI3K/AKT pathway, were implicated in the insulin-induced disruptions during the decidualization process. Moreover, the endometrium of PCOS models showed significantly elevated levels of phosphorylated (Ser473) AKT, with a corresponding reduction in Nr4a1 protein.
conclusionsOur research demonstrates that insulin negatively regulates decidualization in hESC via the PI3K/AKT-NR4A pathway. In vivo analysis revealed a significant dysregulation of the AKT-NR4A1 pathway in the endometrium of PCOS rats. These findings offer novel insights into the pathogenesis of infertility and endometrial disorders associated with hyperinsulinemia in PCOS.
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