Excess sucrose intake during pregnancy programs fetal brain glucocorticoid receptor expression in female but not male C57Bl/6J mice.

Background: Sex-specific mechanisms explaining the association between mothers with obesity and the development of obesity in children are poorly characterized. Permanent changes in fetal brain glucocorticoid receptor (GR) expression caused by exposure to overnutrition may program aberrant energy homeostasis, thereby predisposing the offspring to obesity. This study explores sex differences in brain GR expression using an established mouse model of overnutrition during pregnancy.

Methods: Female C57Bl/6J mice were fed control (CON) or high-fat-high-sucrose (HFHS) diets. Dam cholesterol, insulin, and triglycerides were measured by colorimetric assays. Fetal corticosterone exposure was measured by placental , , , and brain (GR); expression measured by RT-qPCR.

Results: Female, but not male, HFHS fetuses had 46% decreased brain GR and twofold increased expression. There was decreased and but not expression in HFHS placentas. Caloric and sucrose intake, but not fat intake, in dams inversely correlated with fetal GR expression in both sexes. Excess sucrose consumption by dams inversely correlated with female fetal GR and directly correlated with female fetal expression.

Conclusions: Excess sucrose consumption in pregnant dams caused lower GR and higher expression in the female fetal brain. Clinical investigation of excess sucrose intake during pregnancy and its subsequent effect on hypothalamic-pituitary-adrenal axis activity and appetite in offspring may lead to novel, sex-specific obesity prevention strategies in the development of obesity in children.