Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, Hefei, China.
Reproduction. 2021 Jun 7;162(1):73-82. doi: 10.1530/REP-20-0643.
Emerging evidence has demonstrated that melatonin (MT) plays a crucial role in regulating mammalian reproductive functions. It has been reported that MT has a protective effect on polycystic ovary syndrome (PCOS). However, the protective mechanisms of MT remain poorly understood. This study aims to explore the effect of MT on ovarian function in PCOS and to elucidate the relevant molecular mechanisms in vivo and in vitro. We first analysed MT expression levels in the follicular fluid of PCOS patients. A significant reduction in MT expression levels was noted in PCOS patients. Intriguingly, reduced MT levels correlated with serum testosterone and inflammatory cytokine levels in follicular fluid. Moreover, we confirmed the protective function of MT through regulating autophagy in a DHEA-induced PCOS rat model. Autophagy was activated in the ovarian tissue of the PCOS rat model, whereas additional MT inhibited autophagy by increasing PI3K--Akt pathway expression. In addition, serum-free testosterone, inflammatory and apoptosis indexes were reduced after MT supplementation. Furthermore, we also found that MT suppressed autophagy and apoptosis by activating the PI3K-Akt pathway in the DHEA-exposed human granulosa cell line KGN. Our study showed that MT ameliorated ovarian dysfunction by regulating autophagy in DHEA-induced PCOS via the PI3K-Akt pathway, revealing a potential therapeutic drug target for PCOS.
新出现的证据表明，褪黑素（MT）在调节哺乳动物生殖功能方面起着至关重要的作用。据报道，MT 对多囊卵巢综合征（PCOS）具有保护作用。然而，MT 的保护机制仍知之甚少。本研究旨在探讨 MT 对 PCOS 卵巢功能的影响，并在体内和体外阐明相关的分子机制。我们首先分析了 PCOS 患者卵泡液中的 MT 表达水平。结果发现，PCOS 患者的 MT 表达水平显著降低。有趣的是，MT 水平降低与卵泡液中的血清睾酮和炎症细胞因子水平相关。此外，我们通过调节 DHEA 诱导的 PCOS 大鼠模型中的自噬证实了 MT 的保护作用。在 PCOS 大鼠模型的卵巢组织中，自噬被激活，而额外的 MT 通过增加 PI3K--Akt 通路表达来抑制自噬。此外，MT 补充后，血清游离睾酮、炎症和凋亡指数降低。此外，我们还发现 MT 通过激活 DHEA 暴露的人颗粒细胞系 KGN 中的 PI3K-Akt 通路来抑制自噬和凋亡。我们的研究表明，MT 通过 PI3K-Akt 通路调节 DHEA 诱导的 PCOS 中的自噬来改善卵巢功能，为 PCOS 提供了一种潜在的治疗药物靶点。
