Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function.

The perinatal environment is a powerful determinant of risk for developing disease in later life. Here, we have shown that maternal undernutrition causes dramatic changes in heart structure and hypothalamo-pituitary-adrenal (HPA) function across two generations. Pregnant guinea pigs were fed 70% of normal intake from gestational days 1-35 (early restriction; ER), or 36-70 (late restriction; LR). Female offspring (F(1)) were mated and fed ad libitum to create second generation (F(2)) offspring. Heart morphology, blood pressure, baroreceptor and HPA function were assessed in male F(1) and F(2) offspring. ER(F1) males exhibited elevated blood pressure, increased left ventricular (LV) wall thickness and LV mass. These LV effects were maintained in the ER(F2) offspring. Maternal undernutrition increased basal cortisol and altered HPA responsiveness to challenge in both generations; effects were greatest in LR groups. In conclusion, moderate maternal undernutrition profoundly modifies heart structure and HPA function in adult male offspring for two generations.