Vitamin D3 affects mitochondrial biogenesis through mitogen-activated protein kinase in polycystic ovary syndrome mouse model

Safaei, Z. and Bakhshalizadeh, S. and Nasr-Esfahani, M.H. and Akbari Sene, A. and Najafzadeh, V. and Soleimani, M. and Shirazi, R. (2020) Vitamin D3 affects mitochondrial biogenesis through mitogen-activated protein kinase in polycystic ovary syndrome mouse model. Journal of Cellular Physiology, 235 (9). pp. 6113-6126.

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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-induced mouse model. Vitamin D3 applies its effect via the mitogen-activated pathway kinase-extracellular signal-regulated kinases (MAPK-ERK1/2) 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-time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2�, 7�-dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-α and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B-cell lymphoma-2) 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-treated 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-induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA-induced PCOS mice which yet to be investigated. © 2020 Wiley Periodicals, Inc.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: 2',7' dichlorofluorescein diacetate; calcitriol; catalase; fluorescein diacetate; glutathione peroxidase; mitogen activated protein kinase; mitogen activated protein kinase 1; mitogen activated protein kinase 3; mitogen activated protein kinase inhibitor; nuclear respiratory factor; peroxisome proliferator activated receptor gamma coactivator 1alpha; prasterone; reactive oxygen metabolite; superoxide dismutase; unclassified drug; uncoupling protein 2, animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; b cell lymphoma 2 gene; concentration response; controlled study; enzyme phosphorylation; female; gene; gene expression; gene expression level; granulosa cell; mitochondrial biogenesis; mouse; nonhuman; ovary polycystic disease; priority journal; real time polymerase chain reaction; upregulation; Western blotting
Subjects: QV Pharmacology
Depositing User: eprints admin
Date Deposited: 12 Jun 2021 05:14
Last Modified: 12 Jun 2021 05:14

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