SOD2 deficiency-induced oxidative stress attenuates steroidogenesis in mouse ovarian granulosa cells.

Citation
Zaidi, S. K., et al. “Sod2 Deficiency-Induced Oxidative Stress Attenuates Steroidogenesis In Mouse Ovarian Granulosa Cells.”. Molecular And Cellular Endocrinology, p. 110888.
Center Stanford University
Author Syed Kashif Zaidi, Wen-Jun Shen, Yuan Cortez, Stefanie Bittner, Alex Bittner, Sara Arshad, Ting-Ting Huang, Fredric B Kraemer, Salman Azhar
Keywords antioxidant enzymes, Estradiol, lipid peroxidation, Progestin, reactive oxygen species (ROS), StAR protein
Abstract

This study investigated the effects of SOD2 (MnSOD)-deficiency-induced excessive oxidative stress on ovarian steroidogenesis in vivo and isolated and cultured granulosa cells using WT and Sod2+/- mice. Basal and 48 h eCG-stimulated plasma progesterone levels were decreased ~50% in female Sod2+/- mice, whereas plasma progesterone levels were decreased ~70% in Sod2+/- mice after sequential stimulation with eCG followed by hCG. Sod2+/- deficiency caused about 50% reduction in SOD2 activity in granulosa cells. SOD2-deficiency also caused a marked reduction in progestins and estradiol in isolated granulosa cells. qRT-PCR measurements indicated that the mRNA expression levels of StAR protein and steroidogenic enzymes are decreased in the ovaries of Sod2+/- mice. Further studies showed a defect in the movement of mobilized cytosolic cholesterol to mitochondria. The ovarian membrane from Sod2+/- mice showed higher susceptibility to lipid peroxidation. These data indicates that SOD2-deficiency induced oxidative stress inhibits ovarian granulosa cell steroidogenesis primarily by interfering with cholesterol transport to mitochondria and attenuating the expression of Star protein gene and key steroidogenic enzyme genes.

Year of Publication
2021
Journal
Molecular and cellular endocrinology
Volume
519
Number of Pages
110888
Date Published
12/2021
ISSN Number
1872-8057
DOI
10.1016/j.mce.2020.110888
Alternate Journal
Mol Cell Endocrinol
PMID
32717420