A rodent model of low- to moderate-dose ethanol consumption during pregnancy: patterns of ethanol consumption and effects on fetal and offspring growth.

It is unknown whether low to moderate maternal alcohol consumption adversely affects postnatal health. The aim of the present study was to develop a rodent model of low-moderate-dose prenatal ethanol (EtOH) exposure. Sprague-Dawley rats were fed a liquid diet with or without 6% v/v EtOH throughout gestation and the pattern of dietary consumption determined. Fetal bodyweights and hepatic alcohol-metabolising gene expression were measured on embryonic Day (E) 20 and offspring growth studied until 1 year. At E8 the plasma EtOH concentration was 0.03%. There was little difference in dietary consumption between the two treatment groups. At E20, EtOH-exposed fetuses were significantly lighter than controls and had significantly decreased ADH4 and increased CYP2E1 gene expression. Offspring killed on postnatal Day (PN) 30 did not exhibit any growth deficits. Longitudinal repeated measures of offspring growth demonstrated slower growth in males from EtOH-fed dams between 7 and 12 months of age; a cohort of male pups killed at 8 months of age had a reduced crown-rump length and kidney weight. In conclusion, a liquid diet of 6% v/v EtOH fed to pregnant dams throughout gestation caused a 3-8% reduction in fetal growth and brain sparing, with growth differences observed in male offspring later in life. This model will be useful for future studies on the effects of low-moderate EtOH on the developmental origins of health and disease.

Prenatal glucocorticoid exposure in the sheep alters renal development in utero: implications for adult renal function and blood pressure control.

Treatment of the pregnant ewe with glucocorticoids early in pregnancy results in offspring with hypertension. This study examined whether glucocorticoids can reduce nephron formation or alter gene expression for sodium channels in the late gestation fetus. Sodium channel expression was also examined in 2-mo-old lambs, while arterial pressure and renal function was examined in adult female offspring before and during 6 wk of increased dietary salt intake. Pregnant ewes were treated with saline (SAL), dexamethasone (DEX; 0.48 mg/h) or cortisol (CORT; 5 mg/h) over days 26-28 of gestation (term = 150 days). At 140 days of gestation, glomerular number in CORT and DEX animals was 40 and 25% less, respectively, compared with SAL controls. Real-time PCR showed greater gene expression for the epithelial sodium channel (α-, ß-, γ-subunits) and Na(+)-K(+)-ATPase (α-, ß-, γ-subunits) in both the DEX and CORT group fetal kidneys compared with the SAL group with some of these changes persisting in 2-mo-old female offspring. In adulthood, sheep treated with dexamethasone or cortisol in utero had elevated arterial pressure and an apparent increase in single nephron glomerular filtration rate, but global renal hemodynamics and excretory function were normal and arterial pressure was not salt sensitive. Our findings show that the nephron-deficit in sheep exposed to glucocorticoids in utero is acquired before birth, so it is a potential cause, rather than a consequence, of their elevated arterial pressure in adulthood. Upregulation of sodium channels in these animals could provide a mechanistic link to sustained increases in arterial pressure in cortisol- and dexamethasone-exposed sheep, since it would be expected to promote salt and water retention during the postnatal period.