The role of uterus mitochondrial function in high-fat diet-related adverse pregnancy outcomes and protection by resveratrol
Xizi Yang, Ruizhi Hu, Liping Yao, Wentao Zhang, Mingkun Shi, Jiatai Gong, Xupeng Yuan, Yanli Li, Jiahao Yan, Ying Wang, Qian-Jin Zhang, Ziyu He, De‐Xing Hou, Zhiyong Fan, Hongfu Zhang, Liang Chen, Xi He, Jianhua He, Shusong Wu
Abstract
This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.