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.
Bertram
Caroline
C
1Centre for Developmental Origins of Health and Disease, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK.
Khan
Omar
O
Ohri
Sunil
S
Phillips
David I
DI
Matthews
Stephen G
SG
Hanson
Mark A
MA
D000818:Animals; D031204:Caloric Restriction / Q000379:methods*; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*