Stress in pregnancy alters hepatic unfolded protein responses in male adult offspring

Abstract

Stress is considered an independent risk factor for the development of cardiometabolic disorders, especially when it occurs during pregnancy, and it may play an important role in stress-induced fetal programming on the protein-folding homeostasis in hepatic endoplasmic reticulum. The study aimed to determine the effects of prenatal stress on the unfolded protein responses in the liver of male and female offspring of Wistar rats. Pregnant Wistar rats at 90 days old were divided into control and stress groups. The unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. The offspring of each group were divided into four groups according to sex and intervention. After the lactation period, the dams were anesthetized and euthanized for blood collection to determine plasma corticosterone levels. At 90 days old, the offspring were anesthetized and euthanized for liver tissue collection to measure protein expression of the endoplasmic reticulum stress. Dams submitted to prenatal stress showed an increase in corticosterone levels when compared to the control group. In the male offspring, prenatal stress induced lower body mass at birth and at 90 days compared to control, while females presented lower body mass only at birth. Prenatal stress reduced eIF2α expression in males, while increased p-eIF2α expression similarly in both sexes. Furthermore, only males had a greater p-eIF2α/eIF2α ratio and androgen receptor expression when compared to its respective control group and females. Prenatal stress induced a hepatic programming in the reticulum endoplasmic responses only in males at 90 days old by increasing androgen receptor, eIF2α phosphorylation and activity, while in females stress during pregnancy reduced cHDL and had little impact on hepatic unfolded protein response.