Center for Reproductive Medicine, Shantou University Medical College, Shantou 515041, China.
Department of Obstetrics and Gynecology, University of Groningen, University Medical Centre Groningen, 9700 RB Groningen, Netherlands.
Oxid Med Cell Longev. 2022 Nov 3;2022:1070968. doi: 10.1155/2022/1070968. eCollection 2022.
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 (, , , , , and ). 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 M, 24 h) to induce oxidative stress, after which upregulation of , , , , and and downregulation of were observed ( < 0.05). In an aging model, KGN cells were continuously cultured for 3 months, leading to increased expressions of all genes ( < 0.05). In GCs of reproductively aged (8-month-old) Kunming mice, upregulated expression of , , , and and downregulated expression of and were observed ( < 0.01). We therefore here identify a six-gene GC signature associated with oxidative stress and ovarian aging.
卵巢衰老与生育能力下降有关。颗粒细胞（GCs）的氧化应激增加是一个重要的贡献因素。因此，我们想知道在与卵巢衰老相关的 GCs 中是否存在与氧化应激相关的基因特征。我们对公共非人类灵长类动物（NHP）单细胞转录组进行了处理，以鉴定 GC 簇。然后，基于六个与氧化应激相关的差异表达基因（、、、、、），建立了一个与卵巢衰老相关的 GC 特征。ROC 分析在 NHP 单细胞和人类批量转录组数据集中均证实了良好的区分能力。使用 qPCR 在人卵巢颗粒样肿瘤细胞系（KGN）和小鼠 GCs 中研究了基因表达水平。在氧化应激模型中，用亚甲萘醌（7.5μM，24 小时）处理 KGN 细胞以诱导氧化应激，随后观察到、、、、和 的上调和 的下调（<0.05）。在衰老模型中，KGN 细胞连续培养 3 个月，导致所有基因的表达增加（<0.05）。在生殖衰老（8 月龄）昆明小鼠的 GCs 中，观察到、、、和 的上调表达和、和 的下调表达（<0.01）。因此，我们在这里确定了一个与氧化应激和卵巢衰老相关的六个基因 GC 特征。
