Redox profile and mediators of the unfolded protein response (UPR) in the placenta of rats during pregnancy.

Abstract

Proliferation, differentiation, migration and apoptosis of trophoblastic cells are influenced by hypoxia, as well as adequate modulation of oxidative stress and the unfolded protein response (UPR) pathway. We aimed to evaluate the expression profile of redox and UPR mediators in the placenta of rats throughout pregnancy. Placental expression of hypoxia-inducible factor 1α (HIF1α), 8-Hydroxy-2'-deoxyguanosine (8-OHdG), superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), catalase (Cat), activating transcription factor 6 (ATF6), protein kinase RNA-like endoplasmic reticulum kinase (PERK), 78 kD glucose-regulated protein (GRP78) and C/EBP-homologous protein (CHOP), as well as reactive oxygen species (ROS) and peroxynitrite production, were evaluated in Wistar rats on the 10th, 12th, 14th, 16th and 18th day of pregnancy (DP). Increased immunostaining of HIF1α was observed on the 16th and 18th DP, while 8-OHdG and ROS production were greater on the 14th DP. SOD1 and Cat had increased immunostaining on the 14th and 18th DP, while staining of GPX1/2, GRP78 and CHOP was greater on the 18th DP. With regard to gene expression, Hif1α and Sod1 showed increased mRNA expression on the 12th and 16th DP, while Gpx1 had increased expression on the 10th and 16th DP. Cat, Perk and Grp78 gene expression was greater on the 14th DP, unlike Atf6, which showed greater expression on the 12th DP. In contrast, Chop maintained increased expression from the 12th to the 18th DP. The placental expression of redox and UPR mediators in rats is influenced by gestational age, with greater expression in periods of greater HIF1α and 8-OHdG expression and at the end of the pregnancy. This study provides data on the physiological modulation of redox and UPR mediators during placental development in rats.