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.

The fetal hypothalamic-pituitary-adrenal (HPA) axis has numerous key roles in development. Epidemiological data have linked adverse prenatal nutrition with altered organ development and increased incidence of disease in adult life. We studied HPA axis development in resting and stimulated states in late gestation fetal sheep, following 15% reduction in maternal nutritional intake over the first 70 days of gestation (dGA). Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and response profiles for ACTH and cortisol were determined at 113-116 and 125-127 dGA after administration of corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). At 126-128 dGA cortisol profiles were also determined following ACTH administration. Basal ACTH and cortisol concentrations were not different between C and R fetuses. In R fetuses, ACTH response to CRH+AVP was significantly smaller at 113-116 dGA (P<0·01), and cortisol responses were smaller at both 113-116 dGA (P<0·01) and 125-127 dGA (P<0·0001). Cortisol response to ACTH was also smaller in R fetuses (P<0·001). We conclude that, in late gestation fetal sheep, pituitary and adrenal responsiveness is reduced following modest maternal nutrient restriction in early gestation.

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Human epidemiological and animal experimental studies suggest that maternal undernutrition during pregnancy may alter cardiovascular development of the offspring. The extent to which these effects involve changes in fetal cardiovascular function and whether they are necessarily linked to reduced fetal growth is unknown. In sheep, we investigated the effect of a 15% reduction in maternal global nutrition for the first 70 days of gestation (term = 147 days) on fetal blood pressure development, baroreflex control of fetal heart rate (FHR), and cardiovascular responses to acute hypoxemia in late gestation. Basal mean arterial pressure (P < 0.05), systolic blood pressure (P < 0.05), diastolic blood pressure (P < 0.05), and rate-pressure product (P < 0.001) were significantly lower in fetuses of nutritionally restricted ewes (R) compared with controls (C). FHR was not altered. The operating point for the fetal baroreflex was significantly lower in R fetuses compared with C (P < 0.01), but there was no difference between the groups in the cardiovascular response to hypoxemia. We conclude that mild maternal undernutrition alters fetal cardiovascular development, producing low blood pressure and resetting of baroreflex control mechanisms. This effect occurs without any changes in fetal growth or blood gas status.

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Epidemiological and experimental evidence suggests that maternal undernutrition during pregnancy may alter development of fetal organ systems. We have demonstrated previously that fetal hypothalamicpituitary-adrenal (HPA) axis responses to exogenous corticotropin-releasing hormone (CRH) + arginine vasopressin (AVP), or adrenocorticotrophin hormone (ACTH), are reduced in fetuses of mildly undernourished ewes. To examine these effects further we tested HPA axis responses to acute isocapnic hypoxaemia in fetal sheep at 114-129 days gestation (dGA), following 15% reduction in maternal nutritional intake between 0 and 70 dGA. Fetuses from control (C) and nutrient-restricted (R) ewes were chronically catheterised and plasma ACTH and cortisol responses were determined at 114-115, 120-123 and 126-129 dGA during hypoxaemia (1 h) induced by lowering the maternal inspired Oµ fraction (FI,Oµ). Basal plasma cortisol concentrations and HPA axis responses at 114-115 and 120-123 dGA did not differ between C and R fetuses. At 126-129 dGA, both plasma ACTH (P < 0.01) and cortisol (P < 0.05) responses were smaller in R fetuses compared to C fetuses. Fetal blood gas status, fetal body weight, body proportions and organ weights did not differ between the groups. We conclude that mild maternal undernutrition alters development of the fetal HPA axis producing a reduction in pituitary and adrenal responsiveness to endogenous stimuli.

1. Hypoxaemia during intrauterine life may be important in the development of cardiovascular diseases in later life. Thus it was the aim of this study to investigate the effect of repeated acute hypoxia on the cardiovascular development and growth of the fetus. 2. Fourteen fetal sheep (105-109 days gestational age) were instrumented with amniotic and vascular catheters, an electrocardiogram (ECG) electrode and a flow probe around the femoral artery. Seven animals were given repeated acute isocapnic hypoxaemia (Pa,Oµ reduced to ca. 13 mmHg) for 1 h every day for 14 days and they were compared to seven animals which remained normoxic throughout with respect to fetal mean arterial blood pressure (MAP), fetal heart rate (FHR), and fetal baro-and chemoreflexes. 3. No differences were found between the two groups of fetuses in FHR, MAP, baro-or chemoreflexes, femoral blood flow, femoral vascular resistance or fetal growth. 4. Repeated acute hypoxaemia of a moderate degree over a period of 2 weeks in late gestation does not affect cardiovascular development or growth in the fetal sheep.

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