College of Life Science, Capital Normal University, Beijing 100048, China.
Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Yinchuan 750004, China.
Nutrients. 2024 Sep 13;16(18):3085. doi: 10.3390/nu16183085.
Melatonin, as an endocrine neurotransmitter, can promote the development of the ovary. Meanwhile, it also has protective effect on the ovary as an antioxidant. Thyroid hormone (TH) is essential for normal human reproductive function. Many studies have shown that 3,5,3'-triiodothyronine (T) regulates the development of ovarian granulosa cells. However, little is known about the specific mechanisms by which melatonin combines with T to regulate granulosa cell development. The aim of present study was to investigate the effects and the possible mechanisms of melatonin and T on ovarian granulosa cell development. In the present study, cell development and apoptosis were detected by CCK8, EdU and TUNEL, respectively. The levels of related proteins were analyzed by Western blotting. The results showed that oxidative stress (OS) and reactive oxygen species (ROS) were induced by HO in granulosa cells, and cell apoptosis was also increased accompanied with the decreased cellular proliferation and viability. Melatonin protects granulosa cells from HO-induced apoptosis and OS by downregulating ROS levels, especially in the presence of T. Co-treatment of cell with melatonin and T also promotes the expression of GRP78 and AMH, while inhibiting CHOP, Caspase-3, and P16. It was demonstrated that melatonin alone or in combination with T had positive effect on the development of granulosa cells. In addition, the AMPK/SIRT1 signaling pathway is involved in the process of melatonin/T promoting granulosa cell development.
褪黑素作为一种内分泌神经递质，可促进卵巢发育。同时，作为一种抗氧化剂，它对卵巢也具有保护作用。甲状腺激素（TH）对人类正常生殖功能至关重要。许多研究表明，3,5,3'-三碘甲状腺原氨酸（T）调节卵巢颗粒细胞的发育。然而，褪黑素与 T 结合调节颗粒细胞发育的具体机制知之甚少。本研究旨在探讨褪黑素和 T 对卵巢颗粒细胞发育的影响及其可能的机制。在本研究中，通过 CCK8、EdU 和 TUNEL 分别检测细胞发育和细胞凋亡，通过 Western blot 分析相关蛋白水平。结果表明，HO 在颗粒细胞中诱导氧化应激（OS）和活性氧（ROS），同时伴随着细胞增殖和活力的降低，细胞凋亡也增加。褪黑素通过降低 ROS 水平来保护颗粒细胞免受 HO 诱导的凋亡和 OS，尤其是在存在 T 的情况下。细胞同时用褪黑素和 T 处理也促进 GRP78 和 AMH 的表达，同时抑制 CHOP、Caspase-3 和 P16。结果表明，褪黑素单独或与 T 联合对颗粒细胞的发育有积极作用。此外，AMPK/SIRT1 信号通路参与了褪黑素/T 促进颗粒细胞发育的过程。
