1,721,014 research outputs found
Hepatic glucocorticoid receptor expression in adult sheep following early gestational and / or postnatal undernutrition
No full textIn humans and animals environmental constraints during pre- and postnatal life result in phenotypic changes that can be associated with altered cardiovascular and metabolic disease risk in later life (Barker et al., 2002, Poore et al., 2006). The liver is a key organ in glucose and lipid metabolism and altered maternal diet or body composition are associated with changes in fetal liver blood flow (Haugen et al., 2005). Intrauterine challenges such as hypoxia alter blood flow to left and right lobes of the liver differentially. Maternal gestational low protein diet in rats alters adult hepatic gene expression with different effects between liver lobes (Zhang & Byrne, 2000). The glucocorticoid receptor (GR) is a gene associated with disturbances in cardiovascular and metabolic control. However the interaction between pre- and postnatal environments on hepatic GR is unknown. We investigated the effect of reduced early gestation maternal nutrition and/or early postnatal life undernutrition on the expression of GR in adult sheep liver. Welsh Mountain ewes received 100% (C, n=36) or 50 % of total nutrient requirements (U, n=39) from 1-31 days of gestation, and 100 % thereafter. Offspring were fed ad libitum (CC, n=20; UC, n=19) or to reduce body weight to 85 % of individual target weight from 12 to 25 weeks postnatal age and ad libitum thereafter (CU, n=17; UU, n=21). Each group contained approximately equal numbers of males and females and the ratio of twins to singletons was ~2:1. Offspring were sacrificed at 2.5 years, the livers were harvested and segments from the left and right lobes were frozen in liquid nitrogen. GR mRNA levels were measured by semi quantitative RT-PCR and normalized using the mean of three housekeeping genes (RPL19, ?Actin and GAPDH) selected by use of the geNormTM normalizing kit. All data were analysed by ANOVA. Early life nutrition had no effect on GR mRNA expression. GR mRNA expression was significantly higher in males than females (P<0.001). In both males and females the right liver lobe had higher GR mRNA expression than the left (P<0.001). In females, twins had a higher GR mRNA expression than singletons (P<0.05). We conclude that differences in GR expression between left and right lobes of the liver exist in adult sheep, although early gestation and/or postnatal nutrition did not affect these levels. Our finding of increased GR mRNA expression in males suggests that they may be more sensitive to the adverse effects of excess glucocorticoids
The effect of acute maternal hypoglycaemia on fetal cardiovascular control
No full textAims: To investigate the effect of acute maternal hypoglycaemia
on fetal cardiovascular (CV) function, as a sub-optimal environment
in utero has been implicated in the development of CV disease in
adult life.Subjects: Fetal sheep (n = 7) were studied in utero at 125 and 126
days gestational age (dGA, term = 147 days) following implantation
of vascular catheters and an umbilical cord occluder at 119 dGA.Study design: Fetal CV parameters were measured during a
maternal saline (day 125) and insulin (day 125) infusion. Fetal
CV function was assessed by: (a) generating a dose response
curve to angiotensin II; (b) a 90 sec total umbilical cord occlusion;
(c) administration of phenylephrine to assess baroreflex function.Outcome measures: (a) Area under the mean arterial blood
pressure (MAP) response (AUC) to increasing doses of angiotensin II;
(b) MAP and heart rate (HR) response to cord occlusion;
(c) sensitivity and operating point of the baroreflex response.
Results: Maternal insulin infusion resulted in maternal and fetal
hypoglycaemia. (a) The angiotensin II MAP AUC was not affected
by hypoglycaemia. (b) The increase in MAP and decrease in
HR following a 90 sec cord occlusion was not affected by
hypoglycaemia. (c) Hypoglycaemia resulted in reduced fetal
baroreflex sensitivity (P <0.05, paired t test).Conclusions: Our finding of reduced fetal baroreflex sensitivity
during fetal hypoglycaemia indicates altered CV homeostatic
mechanisms. Such fetal adaptations to a poor intrauterine
environment could contribute towards the development of altered
cardiovascular phenotype in adult life
Pre- and periconceptional nutrient restriction affect coronary vascular reactivity in sheep offspring [In special abstracts issue]
No full textModerate early gestation undernutrition has no effect on kidney size and function in late gestation
No full textEarly gestation undernutrition causes increased expression of myosin light chain kinase in adult sheep coronary arteries [In special abstracts issue]
No full textNon-invasive measures of heart rate variability following intermittent umbilical cord occlusion in the preterm ovine fetus
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