A Short Period of Maternal Nutrient Restriction in Late Gestation Modifies Pituitary-Adrenal Function in Adult Guinea Pig Offspring

Abstract

Altered fetal environment can program the hypophyseal-pituitary-adrenal (HPA) axis development and thus affect endocrine function in later life. We hypothesized that 48 h of maternal nutrient restriction during the period of maximal fetal brain growth alters HPA function in adult offspring and leads to modified blood pressure regulation. Pregnant guinea pigs (n = 15) were deprived of food (water ad libitum) or fed normally (n = 13) on days 50 and 51 of gestation, after which they were all fed normally (birth = 68 days). Carotid artery and jugular vein catheters were implanted in adult guinea pig offspring (day 65). Animals were treated with corticotropin (ACTH_1–24; 0.5 µg/kg), corticotropin-releasing hormone (CRH; 0.5 µg/kg) and insulin (5 units/kg), and pituitary-adrenal responses were measured. Guinea pigs were then euthanized and pituitaries removed for analysis of pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels. There was no effect of prenatal treatment on body weight, blood pressure or heart rate. In male offspring, both basal ACTH (p < 0.007) and basal cortisol (p < 0.05) levels were significantly reduced in animals whose mothers had been nutrient restricted (NR). In contrast, in female offspring, basal plasma ACTH was not different between offspring from NR mothers and controls; however, basal plasma cortisol concentrations were significantly (p < 0.01) elevated at 13.00 h in females born to NR mothers. Responses to HPA challenge were different between offspring from NR mothers and control offspring, and these differences were consistent with alterations in basal adrenocortical function. There was no effect of prenatal treatment on POMC mRNA levels in the pars distalis or pars intermedia. However, GR mRNA levels were significantly (p < 0.05) reduced in adult female offspring born to NR mothers. In conclusion, 48 h of maternal nutrient restriction during pregnancy has a long-term effect on HPA function in adult offspring, and this effect is highly sex specific, but does not result in alteration of blood pressure.

Impact of maternal undernutrition on the hypothalamic–pituitary–adrenal axis responsiveness in sheep at different ages postnatal

“…A well-characterized interaction between gender and puberty on the stress-induced response has recently been reported in rats (Viau et al 2005). The results of the present study do not support the hypothesis that programming of the adult HPA axis is sex specific, as was the case with guinea pigs (Lingas & Matthews 2001) and sheep (Gardner et al 2006). However, the main finding of the present study is that the effects of maternal undernutrition on HPA axis function changes with age, thus highlighting the importance of studying outcome at several different times during the life course.…”

Glucose tolerance at age 58 and the decline of glucose tolerance in comparison with age 50 in people prenatally exposed to the Dutch famine

“…Another mechanism that could explain the association between prenatal exposure to famine and later glucose intolerance involves the hypothalamic-pituitary-adrenal (HPA) axis. Maternal sheep and guinea pigs that were undernourished in late gestation gave birth to offspring in which HPA function was altered in adult life [29,30]. In humans, low birthweight is associated with elevated basal plasma cortisol concentrations and increased adrenocortical responsiveness to adrenocorticotrophin at adult age [31,32].…”

Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring

“…Elevated levels of circulating maternal catecholamines cause vasoconstriction of placental blood vessels, reducing placental blood supply and hence impairing the delivery of oxygen and nutrients to the foetuses. Given that hypoxia and nutrient restriction activate the foetal HPA axis (Edwards & McMillen 2002, Roelfsema et al 2005) and elicit foetal sympathetic-adrenomedullary stress responses (Gu & Jones 1986), these responses may contribute to the foetal programming of HPA axis responsivity and anxiety-like behaviour in the adult offspring , Lingas & Matthews 2001, Nunez et al 2008, Fan et al 2009, Wang et al 2013. The adrenal medulla also secretes b-endorphin following stress exposure, which may cross the placenta to influence the development of the foetal brain (Sandman et al 1997).…”