Jia Yanping, Ye Mingming, Bukulmez Orhan, Norman Robert J, Liu Wenqiang, Chen Miaoxin
Centre for Assisted Reproduction, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 2699 Gaoke West Road, Pudong District, Shanghai, 201204, China.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Reprod Sci. 2025 Apr 17. doi: 10.1007/s43032-025-01846-2.
Increased risks of obesity and abnormal glucose metabolism were observed in IVF offspring. However, the underlying molecular mechanism was still unclear. As an important post-translational modification (PTM), lysine acetylation changed with the changes in the metabolic environment and usually occurred on metabolic enzymes to regulate metabolic pathways and enzyme activities and participated in the regulation of downstream metabolites. In our previous study, we proved that supplementation of melatonin in the culture medium improved obesity and metabolic dysfunction in IVF mice. In this study, we further demonstrated that elevated levels of protein acetylation in hepatic cells might be associated with impaired glucose metabolism in IVF offspring, and melatonin could significantly reduce the acetylation level and improve the adverse phenotype of IVF mice. More importantly, we discovered that the supplementation of melatonin in the culture medium during in vitro fertilization significantly enhanced the activity of enzymes, especially citrate synthase (CS) and isocitrate dehydrogenase (IDH) which were involved in tricarboxylic acid recycling and played critical roles in glucose metabolism of liver. Thus, our findings elucidated a new perspective on the mechanisms of metabolic reprogramming of IVF mice.
在体外受精（IVF）后代中观察到肥胖和糖代谢异常的风险增加。然而，其潜在的分子机制仍不清楚。作为一种重要的翻译后修饰（PTM），赖氨酸乙酰化随代谢环境的变化而改变，通常发生在代谢酶上，以调节代谢途径和酶活性，并参与下游代谢物的调节。在我们之前的研究中，我们证明在培养基中添加褪黑素可改善IVF小鼠的肥胖和代谢功能障碍。在本研究中，我们进一步证明肝细胞中蛋白质乙酰化水平升高可能与IVF后代的糖代谢受损有关，而褪黑素可显著降低乙酰化水平并改善IVF小鼠的不良表型。更重要的是，我们发现体外受精期间在培养基中添加褪黑素可显著增强酶的活性，尤其是参与三羧酸循环且在肝脏葡萄糖代谢中起关键作用的柠檬酸合酶（CS）和异柠檬酸脱氢酶（IDH）。因此，我们的研究结果阐明了IVF小鼠代谢重编程机制的一个新视角。
