Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome
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Le résumé fourni par la source
Adult rats treated concomitantly with insulin and human chorionic gonadotropin exhibit endocrine, metabolic, and reproductive abnormalities that are very similar to those observed in polycystic ovary syndrome (PCOS) patients. In this study, we used this rat model to assess the effects of metformin on PCOS-related uterine dysfunction. In addition to reducing androgen levels, improving insulin sensitivity, and correcting the reproductive cycle, metformin treatment induced morphological changes in the PCOS-like uterus. At the molecular and cellular levels, metformin normalized the androgen receptor-mediated transcriptional program and restored epithelial-stromal interactions. In contrast to glucose transport, uterine inflammatory gene expression was suppressed through the PI3K-Akt-NFκB network, but without affecting apoptosis. These effects appeared to be independent of AMPK subunit and autophagy-related protein regulation. We found that when metformin treatment partially restored implantation, several implantation-related genes were normalized in the PCOS-like rat uterus. These results improve our understanding of how metformin rescues the disruption of the implantation process due to the uterine defects that result from hyperandrogenism and insulin resistance. Our data provide insights into the molecular and functional clues that might help explain, at least in part, the potential therapeutic options of metformin in PCOS patients with uterine dysfunction.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Metformin Ameliorates Uterine Defects in a Rat Model of Polycystic Ovary Syndrome
- Date Crossref
- 01/04/2017
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Heilongjiang University of Chinese Medicine Department of Obstetrics and Gynecology pays non établi dans la noticeUniversité ou école supérieure
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First Affiliated Hospital of Heilongjiang University of Chinese Medicine pays non établi dans la noticeÉtablissement de santé
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University of Gothenburg Department of Physiology/Endocrinology pays non établi dans la noticeUniversité ou école supérieure
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Shanghai Medical College of Fudan University Department of Integrative Medicine and Neurobiology pays non établi dans la noticeUniversité ou école supérieure
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Institute of Neurobiology pays non établi dans la noticeStructure de recherche
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State Key Laboratory of Medical Neurobiology pays non établi dans la noticeStructure de recherche
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Obstetrics and Gynecology Hospital of Fudan University Department of Gynecology pays non établi dans la noticeÉtablissement de santé
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Sahlgrenska University Hospital Department of Obstetrics and Gynecology pays non établi dans la noticeÉtablissement de santé
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Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases pays non établi dans la noticeStructure de recherche
Department of Obstetrics and Gynecology — Heilongjiang University of Chinese Medicine, First Affiliated Hospital of Heilongjiang University of Chinese Medicine et Department of Physiology/Endocrinology — University of Gothenburg, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.