Maternal stress induced endoplasmic reticulum stress and impaired pancreatic islets' insulin secretion via glucocorticoid receptor upregulation in adult male rat offspring.
Mina SalimiFarzaneh EskandariFateme BinayiAfsaneh EliassiHossein GhanbarianMehdi HedayatiJavad Fahanik-BabaeiMohamad EftekharyRana KeyhanmaneshHomeira ZardoozPublished in: Scientific reports (2022)
Exposure to perinatal (prenatal and/or postnatal) stress is considered as a risk factor for metabolic disorders in later life. Accordingly, this study aimed to investigate the perinatal stress effects on the pancreatic endoplasmic reticulum (ER) stress induction, insulin secretion impairment and WFS1 (wolframin ER transmembrane Glycoprotein, which is involved in ER homeostasis and insulin secretion) expression changes, in rat offspring. According to the dams' period of exposure to variable stress, their male offspring were divided into, control (CTRL); 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. Offspring pancreases were removed for ER extraction and the assessment of ER stress biomarkers, WFS1 gene DNA methylation, and isolated islets' insulin secretion. Glucose tolerance was also tested. In the stressed groups, maternal stress significantly increased plasma corticosterone levels. In PPS, PS, and PPPS groups, maternal stress increased Bip (Hsp70; heat shock protein family A member 4), Chop (Ddit3; DNA- damage inducible transcript3), and WFS1 protein levels in pancreatic extracted ER. Moreover, the islets' insulin secretion and content along with glucose tolerance were impaired in these groups. In PPS, PS, LS and PPPS groups, the pancreatic glucocorticoid receptor (GR) expression increased. Maternal stress did not affect pancreatic WFS1 DNA methylation. Thus, maternal stress, during prenatal period, impaired the islets' insulin secretion and glucose homeostasis in adult male offspring, possibly through the induction of ER stress and GR expression in the pancreas, in this regard the role of WFS1 protein alteration in pancreatic ER should also be considered.
Keyphrases
- stress induced
- pregnancy outcomes
- dna methylation
- dna damage
- preterm birth
- endoplasmic reticulum
- endoplasmic reticulum stress
- poor prognosis
- heat shock protein
- genome wide
- oxidative stress
- gene expression
- cell proliferation
- binding protein
- metabolic syndrome
- skeletal muscle
- copy number
- physical activity
- breast cancer cells
- human milk
- estrogen receptor
- heat shock
- amino acid
- rna seq
- glycemic control
- clinical evaluation