{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:45:07Z","timestamp":1791845107742,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Reproduction Devel"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The possible relationship between dehydroepiandrosterone (DHEA)\u2010induced polycystic ovary syndrome (PCOS) and epigenetic changes (ECs) leading to the impaired oocyte quality, has not been investigated yet. So, this study aimed to provide an insight into the relationship of the impaired oocyte quality with ECs in a mice DHEA\u2010induced PCOS model and to further reveal the effect of metformin treatment. For this purpose, 80 female BALB\/C mice were randomly divided into four equal groups, named as the control, sham, (DHEA) and DHEA\u2009+\u2009Metformin groups. The alterations in acetylation of H4K5 and H4K16, and in methylation of DNA (5MeC) and H3K9 were evaluated using immunocytochemical. Moreover, the expression of Hdac1, Hdac2, Dnmt1, and Dnmt3a genes involved in ECs were analyzed using reverse\u2010transcription polymerase chain reaction. As well, the levels of mitochondrial membrane potential (MMP), oxidative stress (OS), embryo development, ovarian morphology, sexual hormone, ovulatory function, and AMPK\u03b1 phosphorylation activity were compared in all the studied groups. Metformin attenuated the damages induced by DHEA as indicated by the normalized the estrous cycle, the improved ovarian morphology, the decreased sexual hormone and OS levels, and the increased MMP and AMPK\u03b1 phosphorylation levels. In the metformin group, the <jats:italic>Dnmt1<\/jats:italic>, <jats:italic>Dnmt3a<\/jats:italic>, and <jats:italic>Hdac<\/jats:italic>2 genes have significantly upregulated compared to the DHEA group. However, metformin was found to have no effect on the expression level of <jats:italic>Hdac1<\/jats:italic>. In this regard, significant decrease and increase were observed in both the acetylated H4K16 and methylated H3K9 within MII oocytes in the DHEA\u2009+\u2009Metformin group compared with the DHEA group. Our results show that metformin could enhance the developmental competence of PCOS oocytes via reducing OS and ECs.<\/jats:p>","DOI":"10.1002\/mrd.23537","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T06:10:23Z","timestamp":1634796623000},"page":"817-829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Metformin improves epigenetic modification involved in oocyte growth and embryo development in polycystic ovary syndrome mice model"],"prefix":"10.1002","volume":"88","author":[{"given":"Showra","family":"Amani Abkenari","sequence":"first","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leili","family":"Safdarian","sequence":"additional","affiliation":[{"name":"Department of Infertility of Shariati Hospital Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fardin","family":"Amidi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Infertility of Shariati Hospital Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Clinical Research Development Center of Loghman Hakim Hospital Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roya","family":"Aryanpour","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Yasuj University of Medical Science Yasuj Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elnaz","family":"Salahi","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aligholi","family":"Sobhani","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences Tehran Iran"},{"name":"Department of Anatomy, School of Medicine Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","first-page":"61","article-title":"Review on the role of glutathione on oxidative stress and infertility","volume":"22","author":"Adeoye O.","year":"2018","journal-title":"JBRA Assisted Reproduction"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-10-49"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1550233"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220182"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2019.09.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006250-200304000-00029"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119680"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13262"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.28189"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60038-7"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2017.1410591"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-4-16"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00675"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.9.10.11599"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep18858"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0127512"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0122370"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes8060148"},{"issue":"1","key":"e_1_2_10_20_1","first-page":"101","article-title":"Induction of apoptosis and ovarian cyst formation in the mouse ovary by dehydroepiandrosterone (DHEA)","volume":"34","author":"Kim H. 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