Cardiovascular and hypothalamic-pituitary-adrenal axis development in late gestation fetal sheep and young lambs following modest maternal nutrient restriction in early gestation

Abstract

The effect of a 15% reduction in maternal nutrition for the first 70 days of gestation on cardiovascular and hypothalamic–pituitary–adrenal (HPA) axis responses to administration of corticotropin releasing hormone (CRH) + arginine vasopressin (AVP) was studied at 128 0.7 days gestation in fetal sheep and postnatally, at 85 4.5 days in young lambs. The effect on the fetal cardiovascular response to acute hypoxaemia was also examined. Under basal conditions, fetal heart rate (FHR) was reduced (P<0.05) and basal femoral artery vascular resistance (FVR) was increased (P<0.05) in fetuses of dietary-restricted (R) ewes compared with controls (C). Fetal mean arterial pressure (MAP) was similar in both groups. Femoral artery vascular resistance was also greater during hypoxaemia in R fetuses compared with C fetuses (P<0.05), suggesting that chemoreflex mechanisms were augmented in the R group. The fetal ACTH response to CRH + AVP was similar in both groups. However, cortisol responses to CRH + AVP were smaller in R fetuses compared with C fetuses (P<0.05). Postnatally, basal MAP (P<0.05), and ACTH (P<0.01) and cortisol (P<0.001) responses were greater in R lambs compared with C lambs. It was concluded that modest maternal undernutrition during pregnancy alters development of the cardiovascular system, producing elevated blood pressure in postnatal life. Development of the HPA axis is also altered, with reduced activity during fetal life, but increased activity postnatally. The data suggest that the HPA axis may play a role in mediating the elevation of MAP in R lambs.

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

“…No effect on birth body weight has been reported in a number of previous studies in which ewes were fed at 50 or 85% of their requirements at different periods up to 90 days of gestation (Hawkins et al 1999, 2000, Whoorwood et al 2001, Gopalakrishman et al 2004. On the contrary a reduction in the birth body weight was evident in newborn lambs from mothers undernourished from 105 to 115 days of gestation (Bloomfield et al 2003).…”

“…To date, the majority of studies have focused on the effects of maternal undernutrition in late-gestation fetal sheep, which vary from enhanced, when periconceptional undernutrition was imposed (Edwards & McMillen 2002) to reduced pituitary-adrenal response following CRH administration after early-to mid-gestation undernutrition (Hawkins et al 1999(Hawkins et al , 2000. However, the timing and duration of maternal undernutrition required to produce postnatal consequences have received limited study.…”

“…It has been shown that maternal nutritional insults that have no effect on birth weight can have pronounced effects on fetal metabolism (Harding & Johnston 1995) and hormonal responses (Oliver et al 2001), including alterations in fetal hypothalamic adrenal axis function (Hawkins et al 1999(Hawkins et al , 2000. To date, the majority of studies have focused on the effects of maternal undernutrition in late-gestation fetal sheep, which vary from enhanced, when periconceptional undernutrition was imposed (Edwards & McMillen 2002) to reduced pituitary-adrenal response following CRH administration after early-to mid-gestation undernutrition (Hawkins et al 1999(Hawkins et al , 2000.…”

“…Studies examining the impact of maternal nutrient restriction on HPA axis have been mostly limited to the late-gestation fetus or young lambs (Hawkins et al 2000, Edwards & McMillen 2002, Bloomfield et al 2004 and only a few have been undertaken to establish the long-term effects of maternal undernutrition on HPA function in the adult sheep. Brief undernutrition for 10 but not 20 days during late gestation altered the HPA function in adult offspring, further emphasizing the fact that the timing, type, and duration of fetal nutrient restriction are each important in determining the nature of the fetal adaptive responses and their pathophysiological sequelae in later life (Bloomfield et al 2003).…”

“…It has been shown that maternal nutrient restriction, which has no effect on birth weight, can alter the function of the hypothalamic-pituitary-adrenal (HPA) axis (Hawkins et al 1999(Hawkins et al , 2000, which has been suggested to play a role in programming of the later disease (Seckl 1997). Studies examining the impact of maternal nutrient restriction on HPA axis have been mostly limited to the late-gestation fetus or young lambs (Hawkins et al 2000, Edwards & McMillen 2002, Bloomfield et al 2004 and only a few have been undertaken to establish the long-term effects of maternal undernutrition on HPA function in the adult sheep.…”