ArticlePloS one2017
Dysregulation of In Vitro Decidualization of Human Endometrial Stromal Cells by Insulin via Transcriptional Inhibition of Forkhead Box Protein O1.
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 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
- BMAL1 Dysregulation as a Contributing Mechanism Linking Obesity to Oocyte and Endometrial Dysfunction in IVF.International journal of molecular sciences · 2026Review
- Molecular Mechanisms Underlying Reproductive Dysfunction in Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Multi-omics biomarkers in female fertility: from oocyte quality to endometrial receptivity and clinical translation.Biomarker research · 2026Review
- Elevated triglyceride glucose-body mass index is associated with a higher risk of reduced cumulative live birth and adverse pregnancy outcomes in women undergoing assisted reproductive technology: a retrospective cohort study.Frontiers in endocrinology · 2026Observational
- Association Between Metabolic Score for Insulin Resistance (METS-IR) and Risk of Infertility: Evidence from NHANES 2013-2020 and Mendelian Randomization Study.International journal of women's health · 2026Article
- Molecular Regulation of FOXO1 and Its Pathophysiological Significance in Endometriosis: A Narrative Review.Antioxidants (Basel, Switzerland) · 2025Review
- Organoids as powerful models of endometrium epithelium in transcriptomic, cellular and functional mimicry.Cellular and molecular life sciences : CMLS · 2025Review
- Uterine cyclin A2-deficient mice as a model of female early pregnancy loss.The Journal of clinical investigation · 2024Article
- Hyperinsulinemia impairs decidualization via AKT-NR4A1 signaling: new insight into polycystic ovary syndrome (PCOS)-related infertility.Journal of ovarian research · 2024Article
- DHT and Insulin Upregulate Secretion of the Soluble Decoy Receptor of IL-33 From Decidualized Endometrial Stromal Cells.Endocrinology · 2023Article
- ATOH8 Expression Is Regulated by BMP2 and Plays a Key Role in Human Endometrial Stromal Cell Decidualization.Endocrinology · 2023Article
- Enhanced ZBTB16 Levels by Progestin-Only Contraceptives Induces Decidualization and Inflammation.International journal of molecular sciences · 2023Article
- High Glucose Promotes Inflammation and Weakens Placental Defenses againstInternational journal of molecular sciences · 2023Article
- Basigin is necessary for normal decidualization of human uterine stromal cells.Human reproduction (Oxford, England) · 2022Article
- Single-cell analysis of menstrual endometrial tissues defines phenotypes associated with endometriosis.BMC medicine · 2022Article
- The Regulators of Human Endometrial Stromal Cell Decidualization.Biomolecules · 2022Review
- An Update on the Progress of Endometrial Receptivity in Women with Polycystic Ovary Syndrome.Reproductive sciences (Thousand Oaks, Calif.) · 2022Review
- The Translational Role of miRNA in Polycystic Ovary Syndrome: From Bench to Bedside-A Systematic Literature Review.Biomedicines · 2022Review
- C-Peptide Promotes Cell Migration by Controlling Matrix Metallopeptidase-9 Activity Through Direct Regulation of β-Catenin in Human Endometrial Stromal Cells.Frontiers in cell and developmental biology · 2022Article
- Interaction between insulin and androgen signalling in decidualization, cell migration and trophoblast invasion in vitro.Journal of cellular and molecular medicine · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insulin resistance and compensatory hyperinsulinemia are characteristic features of obesity and polycystic ovary syndrome, and both are associated with reduced fertility and implantation. There is little knowledge about the effect of insulin on the decidualization process and previous findings are contradictory. We investigated the effect of insulin on the regulation of forkhead box protein O1 (FOXO1), one of the most important transcription factors during decidualization. Endometrial stromal cells were isolated from six healthy, regularly menstruating women and decidualized in vitro. Gene expression levels of six putative FOXO1 target genes (including insulin-like growth factor binding protein-1 (IGFBP1) and prolactin (PRL)) were measured with Real-Time PCR following FOXO1 inhibition or insulin treatment. PI3K inhibition was used to identify the possible mechanism behind regulation. Subcellular localization of FOXO1 was analyzed with immunofluorescence. All the genes (IGFBP1, CTGF, INSR, DCN, LEFTY2), except prolactin, were evaluated as FOXO1 target genes in decidualizing stromal cells. Insulin caused a significant dose-dependent inhibition of the verified FOXO1 target genes. It was also demonstrated that insulin regulated FOXO1 target genes by transcriptional inactivation and nuclear export of FOXO1 via PI3K pathway. However, insulin did not inhibit the morphological transformation of endometrial stromal cells via transcriptional inactivation of FOXO1. This study provides new insights on the action of insulin on the endometrium via regulation of FOXO1. It is suggested that hyperinsulinemia results in dysregulation of a high number of FOXO1 controlled genes that may contribute to endometrial dysfunction and reproductive failure. Our findings may illuminate possible reasons for unexplained infertility.
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Registered trials
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