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

Abstract

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.

Maternal influences on epigenetic programming of the developing hypothalamic‐pituitary‐adrenal axis

“…Female rats born small-for-gestational age (SGA) were more likely to have SGA infants than mothers that were not born SGA (Klebanoff et al, 1997). In guinea pigs, both the F1 and F2 generations of undernourished F0 mothers showed increased thickness of septal and left ventricular walls of the heart (Bertram et al, 2008). In addition, both F1 and F2 animals had increased basal cortisol and altered HPA stress reactivity.…”

Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders

“…For example, stress during pregnancy results in increased activity in the F2 generation (Wehmer et al, 1970). Maternal malnutrition and synthetic glucocorticoid administration alter HPA axis functions in both the F1 and F2 generations, that can lead to stress-related behavioral phenotypes (Kostaki et al, 2005;Bertram et al, 2008). In some models, stress exposure of the female results in transmission to the F2 generation, but only through F1 males (Morgan and Bale, 2011;Saavedra-Rodriguez and Feig, 2012), suggesting male gamete-mediated F1 to F2 transmission.…”

Sex-Specific Effects of Prenatal Glucocorticoids on Placental Development

“…These stimuli are likely to be mediated via a number of different hormones and immune factors, but glucocorticoids have been singled out as one of the most prevalent factors. Epidemiological and experimental animal studies have revealed that excess glucocorticoids in utero can be linked to the development of diseases such as hypertension [36][37][38][39][40][41][42], depression [43], cardiovascular disease [44], diabetes [45][46] and attention deficit disorders [23,47]. Further, the outcomes or the severity of these diseases are worse if the offspring affected are male [37][38][39][48][49][50][51].…”