Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep

Abstract

Gatford KL, Dalitz PA, Cock ML, Harding R, Owens JA. Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep.

Alcohol exposure during late gestation adversely affects myocardial development with implications for postnatal cardiac function

“…Whether this LV hypertrophy persists postnatally is yet to be elucidated, but if so, it is likely to lead to elevated cardiovascular risk (23). In support of our findings, an apparent increase in relative heart weight has also been described in fetal sheep following acute EtOH exposure on days 116, 117, and 118 of gestation; however, in that study heart weight was preserved in the presence of a significant reduction in fetal body weight (14).…”

“…Previous studies have reported that exposure to EtOH induces apoptosis of cardiomyocytes both in vivo and in vitro (7,30); in addition, reductions in the in vivo circulating concentrations of the cardiomyocyte growth factor, insulin-like growth factor (IGF)-1, have been reported following EtOH exposure (14). We therefore hypothesized that fetal exposure to EtOH during late gestation would adversely impact on the growth and maturation of cardiomyocytes, as a result of an increase in apoptotic activity and a decrease in IGF expression, leading to a reduction in the complement of cardiomyocytes at birth; we also expected increased extracellular matrix deposition in the myocardium because EtOH increases fibrosis in the adult heart (29,34).…”

Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep

“…A recent study of ethanol exposure in pregnant sheep, involving administration of the same daily maternal ethanol dosing regimen as in the present study from 116 to 118 DGA, found a 19% decrease in fetal body weight associated with transient suppression of maternal plasma IGF1 concentration (35%) and fetal plasma IGF2 concentration (28%) (19). The authors attributed the decreased fetal body weight to the suppression of maternal and fetal IGF concentrations.…”

“…In the present study, although the period of alcohol exposure was much longer, we did not find any reduction in fetal body weight, fetal kidney weight, or fetal renal expression of IGF1 or IGF2. While we have not measured maternal and fetal plasma IGFs, a comparison of the present study with that of Gatford et al (19) suggests that fetal exposure to ethanol during the third-trimester equivalent over a longer gestational period may have different effects on the IGF system than does short-term exposure. The effects on fetal growth are also likely to be dependent on the fetal BEC and the stage of gestation during which exposure occurs (1).…”

Repeated betamethasone treatment of pregnant sheep programs persistent reductions in circulating IGF-I and IGF-binding proteins in progeny

“…Given the lack of IGF-I suppression in response to cortisol, we suggest that effects of repeated betamethasone on fetal plasma IGF-I abundance may be indirect and may be a consequence of betamethasone-induced reductions in placental growth and function (6), and possibly nutrient transport, and that this may contribute to persistence of reduced plasma IGF-I abundance to term. Reduced fetal plasma IGF-I concentrations are thus a common feature of several models of fetal growth restriction in the sheep, including surgical restriction of placental growth (43), acute maternal alcohol consumption (22), severe maternal undernutrition (5), and in the present study, repeated in utero exposure to the synthetic glucocorticoid betamethasone.…”