title: Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats.
abstract: Glucocorticoid overexposure during pregnancy programmes offspring physiology and predisposes to later disease. However, any impact of ethologically relevant maternal stress is less clear, yet of physiological importance. Here, we investigated in rats the short- and long-term effects in adult offspring of repeated social stress (exposure to an aggressive lactating female) during late pregnancy on glucose regulation following stress, glucose-insulin homoeostasis and peripheral expression of genes important in regulating glucose and lipid metabolism and glucocorticoid action. Prenatal stress (PNS) was associated with reduced birth weight in female, but not male, offspring. The increase in blood glucose with restraint was exaggerated in adult PNS males compared with controls, but not in females. Oral glucose tolerance testing showed no effects on plasma glucose or insulin concentrations in either sex at 3 months; however, at 6 months, PNS females were hyperinsulinaemic following an oral glucose load. In PNS males, plasma triglyceride concentrations were increased, with reduced hepatic mRNA expression of 5α-reductase and peroxisome proliferator-activated receptor α (Pparα (Ppara)) and a strong trend towards reduced peroxisome proliferator-activated receptor gamma coactivator 1α (Pgc1α (Ppargc1a)) and Pparγ (Pparg) expression, whereas only Pgc1α mRNA was affected in PNS females. Conversely, in subcutaneous fat, PNS reduced mRNA expression of 11β-hydroxysteroid dehydrogenase type 1 (11βhsd1), phosphoenolpyruvate carboxykinase (Pepck (Pck1)), adipose triglyceride lipase (Atgl) and diglyceride acyltransferase 2 (Dgat2) in females, but only Pepck mRNA expression was reduced in PNS males. Thus, prenatal social stress differentially programmes glucose homoeostasis and peripheral metabolism in male and female offspring. These long-term alterations in physiology may increase susceptibility to metabolic disease.
authors: Division of Neurobiology, The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK. p.j.brunton@ed.ac.uk
authors: Paula J
authors: PJ
authors: Brunton
authors: Katie M
authors: KM
authors: Sullivan
authors: David
authors: D
authors: Kerrigan
authors: John A
authors: JA
authors: Russell
authors: Jonathan R
authors: JR
authors: Seckl
authors: Amanda J
authors: AJ
authors: Drake
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D005938:Glucocorticoids; D007328:Insulin; D005947:Glucose