{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T06:26:45Z","timestamp":1790576805397,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T00:00:00Z","timestamp":1581379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Iran University of Medical Sciences and Health Services, Tehran, Iran","award":["29969"],"award-info":[{"award-number":["29969"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhea, anovulation, and hyperandrogenism. Altered mitochondrial biogenesis can result in hyperandrogenism. The goal of this study was to examine the effect of vitamin D3 on mitochondrial biogenesis of the granulosa cells in the PCOS\u2010induced mouse model. Vitamin D3 applies its effect via the mitogen\u2010activated pathway kinase\u2010extracellular signal\u2010regulated kinases (MAPK\u2010ERK1\/2) pathway. The PCOS mouse model was induced by the injection of dehydroepiandrosterone (DHEA). Isolated granulosa cells were subsequently treated with vitamin D3, MAPK activator, and MAPK inhibitor. Gene expression levels were measured using real\u2010time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2\u2032, 7\u2032\u2010dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator\u2010activated receptor gamma coactivator 1\u2010\u03b1 and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B\u2010cell lymphoma\u20102) genes were upregulated in the PCOS mice that treated with vitamin D3 compared with the PCOS mice without any treatment. Vitamin D3 and MAPK activator\u2010treated groups also reduced ROS levels compared with the nontreated PCOS group. In summary, vitamin D3 and MAPK activator increased the levels of mitochondrial biogenesis, MAPK pathway, and mtMP markers, while concomitantly decreased ROS levels in granulosa cells of the PCOS\u2010induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA\u2010induced PCOS mice which yet to be investigated.<\/jats:p>","DOI":"10.1002\/jcp.29540","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T04:44:22Z","timestamp":1581482662000},"page":"6113-6126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Vitamin D3 affects mitochondrial biogenesis through mitogen\u2010activated protein kinase in polycystic ovary syndrome mouse model"],"prefix":"10.1002","volume":"235","author":[{"given":"Zahra","family":"Safaei","sequence":"first","affiliation":[{"name":"Department of Anatomical Sciences, School of Medicine Iran University of Medical Sciences Tehran Iran"},{"name":"Cellular and Molecular Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Bakhshalizadeh","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences, School of Medicine Zanjan University of Medical Sciences Zanjan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Hossein","family":"Nasr\u2010Esfahani","sequence":"additional","affiliation":[{"name":"Department of Cellular Biotechnology, Cell Science Research Center Royan Institute for Biotechnology, ACECR Isfahan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azadeh","family":"Akbari Sene","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Shahid Akbarabadi Hospital IVF Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vahid","family":"Najafzadeh","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Animal Sciences, Anatomy &amp; Biochemistry Section University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoureh","family":"Soleimani","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences, School of Medicine Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3907-079X","authenticated-orcid":false,"given":"Reza","family":"Shirazi","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences, School of Medicine Iran University of Medical Sciences Tehran Iran"},{"name":"Cellular and Molecular Research Center Iran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016340601090337"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/19396368.2017.1296046"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3330"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20100542"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2013.04.002"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-795-2_6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0083402"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2006.05.016"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/01913123.2017.1385668"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms12107199"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00361.2004"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.55.03.06.db05-0453"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2013.04.014"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0967199418000291"},{"issue":"9","key":"e_1_2_10_16_1","doi-asserted-by":"crossref","first-page":"4175","DOI":"10.4049\/jimmunol.160.9.4175","article-title":"Inhibition of mitogen\u2010activated protein kinase kinase blocks T cell proliferation but does not induce or prevent anergy","volume":"160","author":"DeSilva D. 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