We investigated the effects of moderate maternal periconceptional undernutrition from 60 d before to 30 d after mating on fetal hypothalamic-pituitary-adrenal axis function in late gestation. Ewes were sampled regularly during the period of undernutrition for circulating hormone levels. Vascular catheters were inserted into ewes and their singleton fetuses at 112 d gestation (term, 145 d), and fetal ACTH(1-24) and metyrapone challenge tests were performed at 127 and 128 d. Postmortems were performed at 132 d. Fetuses of undernourished ewes (UN, n = 12) had elevated baseline cortisol concentrations (P < 0.05), compared with fetuses of ad libitum-fed ewes (n = 10). There were no differences between groups in fetal responses to ACTH challenge, but only UN fetuses demonstrated ACTH and 11-deoxycortisol responses to metyrapone (P < 0.05). UN fetuses had increased mRNA levels for proopiomelanocortin and prohormone convertase-1, but not -2, in the pars intermedia of the pituitary gland (P < 0.05). Glucocorticoid receptor mRNA levels were not different between groups in pituitary or hypothalamus. Maternal cortisol and ACTH levels during undernutrition were profoundly suppressed (P < 0.001), rather than elevated, in UN ewes. Furthermore, the normal pregnancy rise in maternal serum progesterone concentrations was delayed in undernourished mothers. These data demonstrate that events around the time of conception have profound effects on fetal hypothalamic-pituitary-adrenal development in late gestation and that factors other than fetal exposure to excess glucocorticoids may be important.
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.
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