Evaluation of the effect of prepregnancy, pregnancy and lactation stress on ER stress, WFS1 and GLUT-2 expressions and methylation and insulin secretion of pancreatic isolated Langerhans islets in male rat offspring

Abstract

Growing evidences have demonstrated that adversity in early-life, especially in the prenatal and postnatal periods, may change the programming of many body systems and cause the incidence of different disorders in later life. Accordingly, this study aimed to investigate the effect of pre-pregnancy, pregnancy and lactation stress on ER stress, WFS1 expressions and methylation and insulin secretion of pancreatic isolated Langerhans islets in male rat offspring Materials and Methods: Based on the maternal exposure to variable stress throughout perinatal periods, the pups were divided into 8 groups including control (C); pre-pregnancy, pregnancy, lactation stress (PPPLS); pre-pregnancy stress (PPS); pregnancy stress (PS); lactation stress (LS); pre-pregnancy, pregnancy stress (PPPS); pregnancy, lactation stress (PLS); pre-pregnancy, lactation stress (PPLS) groups (n=? for each). Following an overnight fasting at postnatal day (PND) 64, blood samples were taken and performed oral glucose tolerance test (OGTT). The pancreas of each was used for ER extraction and ER stress biomarkers assessment, WFS1 gene DNA methylation, isolated islets’ insulin secretion, GLUT-2 protein level, lipid peroxidation and antioxidant status, and number of beta cells in the pancreatic islets of Langerhans. In addition, the levels of plasma corticosterone were determined in different groups of mothers and offspring. Results: plasma corticosterone levels in the stressed groups increased (p<0.01 to p<0.001). Maternal stress raised MDA concentrations and reduced the activities of antioxidant enzymes in plasma and pancreas compared to control group (p<0.05 to p<0.001). Moreover, GLUT-2 protein levels and number of beta cells in stress groups declined compared to controls (p<0.05 to p<0.001). Bip, Chop, and WFS1 mRNA and protein levels in pancreatic extracted ER of PPS, PS, and PPPS groups elevated and the insulin secretion and content of islets’ impaired along with glucose tolerance (p<0.05 to p<0.001). The expression levels of pancreatic glucocorticoid receptor (GR) increased in PPS, PS, LS and PPPS groups (p<0.05 to p<0.001). Maternal stress did not affect WFS1 DNA methylation.