Jin Jun-Xue, Sun Jing-Tao, Jiang Chao-Qian, Cui Hong-Di, Bian Ya, Lee Sanghoon, Zhang Lianjin, Lee Byeong Chun, Liu Zhong-Hua
Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Antioxidants (Basel). 2022 Mar 31;11(4):687. doi: 10.3390/antiox11040687.
Previous studies suggest that the inclusion of melatonin (MTn) in in vitro maturation protocols improves the developmental competence of oocytes by scavenging reactive oxygen species (ROS). However, the molecular mechanisms integrating melatonin receptor (MT)-mediated lipid metabolism and redox signaling during in vitro cumulus-oocyte complex (COC) development still remain unclear. Here, we aimed to elucidate the potential role of MTn receptors in lipid metabolic adjustments during in vitro porcine COC development. We observed that MTn-mediated Gα-cAMP/PKA signaling facilitated lipolysis primarily through the MT2 receptor and subsequently increased fatty acid (FA) release by hydrolyzing intracellular triglycerides (TGs) in cumulus cells. Furthermore, was a critical FA transporter that transported available FAs from cumulus cells to oocytes and promoted de novo TG synthesis in the latter. In addition, MTn regulated lipogenesis and intracellular lipolysis to maintain lipid homeostasis and limit ROS production, thereby supporting oocyte cytoplasmic maturation and the subsequent embryo development. Taken together, these findings provide insight into the possible mechanism integrating MT2-mediated lipid homeostasis and redox signaling, which limits ROS production during in vitro COC development. Therefore, understanding the dynamics of the interactions between lipid homeostasis and redox signaling driven by MT2 is necessary in order to predict drug targets and the effects of therapeutics used to improve female reproductive health.
先前的研究表明，在体外成熟培养方案中添加褪黑素（MTn）可通过清除活性氧（ROS）来提高卵母细胞的发育能力。然而，在体外卵丘-卵母细胞复合体（COC）发育过程中，整合褪黑素受体（MT）介导的脂质代谢和氧化还原信号的分子机制仍不清楚。在此，我们旨在阐明MTn受体在体外猪COC发育过程中脂质代谢调节中的潜在作用。我们观察到，MTn介导的Gα-环磷酸腺苷/蛋白激酶A信号主要通过MT2受体促进脂肪分解，随后通过水解卵丘细胞内的甘油三酯（TGs）增加脂肪酸（FA）释放。此外， 是一种关键的FA转运蛋白，它将可用的FAs从卵丘细胞转运到卵母细胞，并促进后者的从头合成TG。此外，MTn调节脂肪生成和细胞内脂肪分解以维持脂质稳态并限制ROS产生，从而支持卵母细胞的细胞质成熟和随后的胚胎发育。综上所述，这些发现为整合MT2介导的脂质稳态和氧化还原信号的可能机制提供了见解，该机制在体外COC发育过程中限制了ROS的产生。因此，了解由MT2驱动的脂质稳态和氧化还原信号之间相互作用的动态过程对于预测用于改善女性生殖健康的药物靶点和治疗效果是必要的。
