An Oxidative Stress-Related Gene Signature in Granulosa Cells Is Associated with Ovarian Aging. (3rd November 2022)

• Record Type: Journal Article
• Authors: Lin, Nuan; Lin, Jiazhe; Plosch, Torsten; Sun, Pingnan; Zhou, Xiaoling
• Other Names: Moreno Sandra Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2022(2022)
• Publication Date: 2022-11-03
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2022/1070968
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Ovarian aging is associated with a decrease in fecundity. Increased oxidative stress of granulosa cells (GCs) is an important contributor. We thus asked whether there is an oxidative stress-related gene signature in GCs associated with ovarian aging. Public nonhuman primate (NHP) single-cell transcriptome was processed to identify GC cluster. Then, a GC signature for ovarian aging was established based on six oxidative stress-related differentially expressed genes ( MAPK1, STK24, AREG, ATG7, ANXA1, and PON2 ). Receiver operating characteristic (ROC) analysis confirmed good discriminating capacity in both NHP single-cell and human bulk transcriptome datasets. Gene expression levels were investigated using qPCR in the human ovarian granulosa-like tumor cell line (KGN) and mouse GCs. In an oxidative stress model, KGN cells were treated with menadione (7.5 μ M, 24 h) to induce oxidative stress, after which upregulation of MAPK1, STK24, ATG7, ANXA1, and PON2 and downregulation of AREG were observed (p < 0.05 ). In an aging model, KGN cells were continuously cultured for 3 months, leading to increased expressions of all genes (p < 0.05 ). In GCs of reproductively aged (8-month-old) Kunming mice, upregulated expression of Mapk1, Stk24, Atg7, and Pon2 and downregulated expression of Anxa1 and Areg were observed (p < 0.01 ). We therefore here identify a six-gene GC signature associated with oxidative stress and ovarian aging.