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

Overview

Journal Int J Fertil Steril

Specialty Reproductive Medicine

Date 2020 Jul 19

PMID 32681627

Citations 13

Authors

Zahra Safaei

S Habnam Bakhshalizadeh

Mohammad Hossein Nasr Esfahani

Azadeh Akbari Sene

Vahid Najafzadeh

Mansoureh Soleimani

Reza Shirazi

Affiliations

Soon will be listed here.

Abstract

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 cause infertility. Since vitamin D3 has been shown to improve the PCOS symptoms, the aim of study was to investigate the effects vitamin D3 on copy number, mitochondrial biogenesis, and membrane integrity of granulosa cells in a 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 three groups: 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 compared between different groups using real-time PCR. copy number was also investigated by qPCR. The mitochondrial structure was evaluated by transmission electron microscopy (TEM). Hormonal levels were measured by an enzymelinked immunosorbent assay (ELISA) kit.

Results: The numbers of pre-antral and antral follicles increased in PCOS group in comparison with the non-PCOS group. Mitochondrial biogenesis genes were downregulated in granulosa cells of PCOS mice when compared to the non-PCOS granulosa cells. However, treatment with vitamin D3 increased expression levels of these genes compared to PCOS granulosa cells with no treatments. Most of the mitochondria in the PCOS group were spherical with almost no cristae. Our results showed that in the PCOS group treated with vitamin D3, the copy number increased significantly in comparison to PCOS granulosa cells with no treatments.

Conclusion: According to this study, we can conclude, vitamin D3 improves mitochondrial biogenesis and membrane integrity, mtDNA copy number in granulosa cells of PCOS mice which might improve follicular development and subsequently oocyte quality.

Citing Articles

Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome.

van Tienhoven X, Ruiz de Chavez Gascon J, Cano-Herrera G, Sarkis Nehme J, Souroujon Torun A, Bautista Gonzalez M Int J Mol Sci. 2025; 26(5).

PMID: 40076878 PMC: 11899835. DOI: 10.3390/ijms26052256.

Oxidative stress and energy metabolism abnormalities in polycystic ovary syndrome: from mechanisms to therapeutic strategies.

Yan H, Wang L, Zhang G, Li N, Zhao Y, Liu J Reprod Biol Endocrinol. 2024; 22(1):159.

PMID: 39722030 PMC: 11670460. DOI: 10.1186/s12958-024-01337-0.

Connecting the dots: the role of fatigue in female infertility.

Li W, Huang X, Wei Y, Yin T, Diao L Reprod Biol Endocrinol. 2024; 22(1):66.

PMID: 38849828 PMC: 11157719. DOI: 10.1186/s12958-024-01235-5.

Mitigating bisphenol A-induced apoptosis in KGN cells: the therapeutic role of 1,25-dihydroxyvitamin D through upregulation of PGC-1α expression and inhibition of the mitochondrial cytochrome c pathway.

Tang L, Du K, Luo K, Wang L, Hua F Hormones (Athens). 2024; 23(3):363-374.

PMID: 38421590 PMC: 11436470. DOI: 10.1007/s42000-024-00539-w.

Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology.

Siemers K, Klein A, Baack M Int J Mol Sci. 2023; 24(17).

PMID: 37685928 PMC: 10488260. DOI: 10.3390/ijms241713123.

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