College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT 05405, USA.
Nutrients. 2018 Sep 1;10(9):1190. doi: 10.3390/nu10091190.
Decreased protein breakdown in pregnant women results in lower concentration of methionine (Met) in plasma, causing pregnancy-related metabolic disturbance. Its dipeptide methionyl-methionine (Met-Met) may exert positive influence in fetal development. This study mainly investigated whether Met-Met can be used as part of free Met to promote reproductive outcomes in mice and the underlying mechanisms. Met-deficient pregnant mice were treated with Met alone or with Met-Met during pregnancy. Daily intraperitoneal injection of 35% dietary Met in pregnant mice was the best dose among the 15⁻45% doses. Embryo development and newborn birth weight were enhanced when 25% of the Met in the 35% Met group was replaced with Met-Met. Met-Met replacement had higher plasma insulin, glucose, and free amino acids (AA) concentrations. Besides, in the placenta, the AA transporter mRNA abundances and peptide transporters (PhT1 and PepT1) protein levels were higher in Met-Met treatment group. Moreover, Met-Met increased 4E-BP1, S6K1 and AKT/mTOR phosphorylation. These results suggest that Met-Met could be used as a partial source of Met to promote reproductive outcomes in Met-restricted pregnant mice, which might be mediated by promoting nutrient availability and activating AKT/mTOR-mediated signaling pathway.
孕妇体内蛋白质分解减少导致血浆中甲硫氨酸（Met）浓度降低，从而引起与妊娠相关的代谢紊乱。其二肽甲硫氨酰-甲硫氨酸（Met-Met）可能对胎儿发育产生积极影响。本研究主要探讨 Met-Met 是否可作为游离 Met 的一部分，促进小鼠的生殖结局及其潜在机制。在妊娠期间，用 Met 或 Met-Met 处理 Met 缺乏的妊娠小鼠。在妊娠小鼠中，每日腹腔注射 35%饮食 Met 的最佳剂量为 15-45%剂量中的 15%。当将 35%Met 组中 25%的 Met 用 Met-Met 替代时，胚胎发育和新生儿出生体重增加。Met-Met 替代可提高血浆胰岛素、葡萄糖和游离氨基酸（AA）浓度。此外，在胎盘组织中，Met-Met 处理组的 AA 转运体 mRNA 丰度和肽转运体（PhT1 和 PepT1）蛋白水平更高。此外，Met-Met 增加了 4E-BP1、S6K1 和 AKT/mTOR 的磷酸化。这些结果表明，Met-Met 可作为 Met 的部分来源，促进 Met 限制的妊娠小鼠的生殖结局，这可能是通过促进营养物质的可用性和激活 AKT/mTOR 介导的信号通路来介导的。
