Reactive oxygen species mediated placental oxidative stress, mitochondrial content, and cell cycle progression through mitogen-activated protein kinases in intrauterine growth restricted pigs.

Intrauterine growth restriction (IUGR) remains a significant obstacle in pig production; however, information regarding the relationship between reactive oxygen species (ROS)-induced placental dysfunction and IUGR is still unknown. This study aimed to explore the placental redox status, mitochondrial content, cellular progression, and mitogen-activated protein kinase (MAPK) pathways in IUGR. Placental tissues were collected from normal intrauterine gestation (NIUG) and IUGR fetuses at delivery. Compared with the NIUG, placental ROS production, lipid peroxidation, and DNA damage were increased in IUGR. Placental mitochondrial DNA (mtDNA) content and mtDNA-encoded gene expression decreased in IUGR. Moreover, p21 phosphorylation increased, cyclin E expression decreased in IUGR cases, which showed senescence characteristics. Analysis of signaling pathways showed that the ERK1/2 phosphorylation increased whereas the p38 and JNK phosphorylation decreased in IUGR. In cultured porcine trophectoderm (pTr) cells, exogenous H2 O2 increased intracellular ROS production, decreased cell viability in a dose-dependent manner. Cell cycle distribution was found to arrest in S and G2/M phases. Our findings suggested that IUGR was associated with greater placental ROS and oxidative injury, which might be a factor that resulted in lower mitochondrial content, microvilli loss and senescence, and activation of MAPK pathways.