Department of Pharmacology, Jinan University, Guangzhou 510632, China.
Department of Cell Biology, Jinan University, Guangzhou 510632, China.
Int J Mol Sci. 2023 Aug 8;24(16):12560. doi: 10.3390/ijms241612560.
The ovary is a highly susceptible organ to senescence, and granulosa cells (GCs) have a crucial role in oocyte development promotion and overall ovarian function maintenance. As age advances, GCs apoptosis and dysfunction escalate, leading to ovarian aging. However, the molecular mechanisms underpinning ovarian aging remain poorly understood. In this study, we observed a correlation between the age-related decline of fertility and elevated expression levels of miR-143-3p in female mice. Moreover, miR-143-3p was highly expressed in senescent ovarian GCs. The overexpression of miR-143-3p in GCs not only hindered their proliferation and induced senescence-associated secretory phenotype (SASP) but also impeded steroid hormone synthesis by targeting ubiquitin-conjugating enzyme E2 E3 () and luteinizing hormone and human chorionic gonadotropin receptor (). These findings suggest that miR-143-3p plays a substantial role in senescence and steroid hormone synthesis in GCs, indicating its potential as a therapeutic target for interventions in the ovarian aging process.
卵巢是一个极易衰老的器官，颗粒细胞 (GCs) 在促进卵母细胞发育和维持整体卵巢功能方面起着至关重要的作用。随着年龄的增长，GCs 的凋亡和功能障碍加剧，导致卵巢衰老。然而，卵巢衰老的分子机制仍知之甚少。在这项研究中，我们观察到雌性小鼠生育能力与 miR-143-3p 表达水平随年龄增长而下降之间存在相关性。此外，miR-143-3p 在衰老的卵巢 GCs 中表达水平升高。GCs 中 miR-143-3p 的过表达不仅阻碍其增殖并诱导衰老相关分泌表型 (SASP)，还通过靶向泛素连接酶 E2 E3 () 和促黄体生成素和人绒毛膜促性腺激素受体 () 抑制类固醇激素合成。这些发现表明，miR-143-3p 在 GCs 的衰老和类固醇激素合成中起着重要作用，表明其作为干预卵巢衰老过程的治疗靶点的潜力。
