Effect of Vitamin D3 on Mitochondrial Biogenesis in Granulosa Cells Derived from Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder diagnosed by anovulation hyperandrogenism.Hyperandrogenism increases apoptosis, which will eventually disturb follicular growth in PCOS patients.Since mitochondria regulate apoptosis, they might be affected by high incidence of follicular atresia. This may causeinfertility. Since vitamin D3 has been shown to improve the PCOS symptoms, the aim of study was to investigate theeffects vitamin D3 on mtDNA copy number, mitochondrial biogenesis, and membrane integrity of granulosa cells ina PCOS-induced mouse model.Materials and Methods: In this experimental study, the PCOS mouse model was induced by dehydroepiandrosterone(DHEA). Granulosa cells after identification by follicle-stimulating hormone receptor (FSHR) were cultured in threegroups: 1. granulosa cells treated with vitamin D3 (100 nM for 24 hours), 2. granulosa cells without any treatments,3. Non-PCOS granulosa cells (control group). Mitochondrial biogenesis gene (TFAM) expression was comparedbetween different groups using real-time PCR. mtDNA copy number was also investigated by qPCR. The mitochondrialstructure was evaluated by transmission electron microscopy (TEM). Hormonal levels were measured by anenzymelinked immunosorbent assay (ELISA) kit.Results: The numbers of pre-antral and antral follicles increased in PCOS group in comparison with the non-PCOSgroup. Mitochondrial biogenesis genes were downregulated in granulosa cells of PCOS mice when compared to thenon-PCOS granulosa cells. However, treatment with vitamin D3 increased mtDNA expression levels of these genescompared to PCOS granulosa cells with no treatments. Most of the mitochondria in the PCOS group were sphericalwith almost no cristae. Our results showed that in the PCOS group treated with vitamin D3, the mtDNA copy numberincreased significantly in comparison to PCOS granulosa cells with no treatments.Conclusion: According to this study, we can conclude, vitamin D3 improves mitochondrial biogenesis and membraneintegrity, mtDNA copy number in granulosa cells of PCOS mice which might improve follicular development andsubsequently oocyte quality.