Abstract：
Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.
摘要：
卵母细胞和胚胎在体内和体外对环境应激高度敏感。在体外培养过程中,许多压力条件会影响胚胎质量和生存能力，导致不良临床结局，如流产和先天性异常。在这项研究中,我们发现戊酸（VA）增加线粒体膜电位和ATP含量，降低了线粒体产生的活性氧的水平，从而改善了猪早期胚胎发育过程中的线粒体功能。VA降低自噬相关因子LC3B和BECLIN1的表达。有趣的是,VA抑制自噬相关磷酸化一磷酸腺苷活化蛋白激酶(p-AMPK)的表达,磷酸化-UNC-51-样自噬激活激酶1(p-ULK1,Ser555),和ATG13，减少细胞凋亡。短链脂肪酸（SCFA）可以通过细胞膜上的G蛋白偶联受体发出信号或通过转运蛋白直接进入细胞。我们进一步表明，单羧酸转运蛋白1（MCT1）对于VA对胚胎质量的影响是必需的，这为SCFA影响胚胎的途径提供了新的分子视角。重要的是,VA通过MCT1显著抑制AMPK-ULK1自噬信号通路,减少细胞凋亡,胚胎多能性基因表达增加，提高胚胎质量。
