Zhu Yuanyuan, Sun Heming, Gao Ting, Hou Shengdi, Li Yuebo, Xu Ying, Zhang Qingxia, Feng Dingqing
Department of Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
Core Unit of National Clinical Research Center for Laboratory Medicine, Hefei, 230001, China.
J Ovarian Res. 2025 Jun 18;18(1):133. doi: 10.1186/s13048-025-01715-1.
The female ovary undergoes constant follicular atresia from birth, as well as ovulation and corpus luteum (CL) regression during reproductive age, leading to recurrent ovarian remodeling and ultimately resulting in ovarian aging. However, aging-related cellular and molecular changes in the ovary remain poorly explored.
Using ovarian transcriptomics, we characterized the changes in gene expression in the ovaries of young (2-month-old), middle-aged (6-month-old) and old (12-month-old) mice. Our analyses revealed that the stromal cell markers THY1 and CD44 were significantly upregulated, whereas the markers of oocytes, granulosa cells and theca cells were markedly downregulated in old mice; thus, endocrine dysfunction occurred. We also found that MAPK pathway- and inflammation response-related genes were enriched and that the populations of Tregs, macrophages and NK cells notably decreased in aged ovaries, which was confirmed by flow cytometry. However, during superovulation, the proportions of macrophages and NK cells steadily increased as the follicles developed and ovulated, whereas the proportion of macrophages sharply decreased after ovulation. We further verified these ovarian changes in specific cell markers and rate-limiting enzymes for steroid hormone synthesis by immunohistochemistry (IHC) and collagen deposition by Masson's trichrome staining in pre- and postmenopausal women.
These results from clinical samples demonstrated that aging-associated changes were similar to those observed in mice and were strongly correlated with the age of the woman. Therefore, this report provides critical insights into aging-related cellular and molecular changes in the ovary.
女性卵巢从出生起就经历持续的卵泡闭锁，在生育年龄还会经历排卵和黄体退化，导致卵巢反复重塑，最终导致卵巢衰老。然而，卵巢中与衰老相关的细胞和分子变化仍未得到充分研究。
我们利用卵巢转录组学技术，对年轻（2月龄）、中年（6月龄）和老年（12月龄）小鼠卵巢中的基因表达变化进行了表征。我们的分析表明，老年小鼠中基质细胞标志物THY1和CD44显著上调，而卵母细胞、颗粒细胞和卵泡膜细胞的标志物则明显下调；因此，出现了内分泌功能障碍。我们还发现丝裂原活化蛋白激酶（MAPK）信号通路和炎症反应相关基因富集，并且老年卵巢中调节性T细胞（Tregs）、巨噬细胞和自然杀伤细胞（NK细胞）的数量显著减少，这一点通过流式细胞术得到了证实。然而，在超排卵过程中，随着卵泡发育和排卵，巨噬细胞和NK细胞的比例稳步增加，而排卵后巨噬细胞的比例急剧下降。我们通过免疫组织化学（IHC）进一步验证了绝经前和绝经后女性卵巢中特定细胞标志物和类固醇激素合成限速酶的这些变化，以及通过Masson三色染色验证了胶原沉积情况。
临床样本的这些结果表明，与衰老相关的变化与在小鼠中观察到的变化相似，并且与女性年龄密切相关。因此，本报告为卵巢中与衰老相关的细胞和分子变化提供了重要见解。
