Prenatal Alcohol Exposure: Foetal Programming, the Hypothalamic‐Pituitary‐Adrenal Axis and Sex Differences in Outcome

Abstract

Prenatal exposure to alcohol has adverse effects on offspring neuroendocrine and behavioural functions. Alcohol readily crosses the placenta, thus directly affecting developing foetal endocrine organs. In addition, alcohol‐induced changes in maternal endocrine function can disrupt the normal hormonal interactions between the pregnant female and foetal systems, altering the normal hormone balance and, indirectly, affecting the development of foetal metabolic, physiological and endocrine functions. The present review focuses on the adverse effects of prenatal alcohol exposure on offspring neuroendocrine function, with particular emphasis on the hypothalamic‐pituitary‐adrenal (HPA) axis, a key player in the stress response. The HPA axis is highly susceptible to programming during foetal and neonatal development. Here, we review data demonstrating that alcohol exposure in utero programmes the foetal HPA axis such that HPA tone is increased throughout life. Importantly, we show that, although alterations in HPA responsiveness and regulation are robust phenomena, occurring in both male and female offspring, sexually dimorphic effects of alcohol are frequently observed. We present updated findings on possible mechanisms underlying differential effects of alcohol on male and female offspring, with special emphasis on effects at different levels of the HPA axis, and on modulatory influences of the hypothalamic–pituitary–gonadal hormones and serotonin. Finally, possible mechanisms underlying foetal programming of the HPA axis, and the long‐term implications of increased exposure to endogenous glucocorticoids for offspring vulnerability to illnesses or disorders later in life are discussed.

Prenatal Exposure to Alcohol Reduces Nephron Number and Raises Blood Pressure in Progeny

“…Prenatal ethanol exposure is known to influence the activity of the hypothalamic-pituitary-adrenal axis and to result in elevated maternal glucocorticoid levels. 40 Thus it is plausible to suggest that the findings observed within this study may be mediated at least in part by the actions of glucocorticoids.…”

An examination of sex differences in the effects of early-life opiate and alcohol exposure

“…Alcohol consumed by the mother can easily pass through the placenta, directly affecting the developing fetus. In addition, alcohol can also indirectly affect the fetus by impacting the mother's critical hormonal balance and placental function [11,12,71]. The developing brain is particularly vulnerable to the toxicological effects of alcohol.…”

Metabolic effects following periconceptional alcohol exposure in rat adult offspring: modulations by a postnatal western diet

“…Alcohol is known to increase maternal levels of glucocorticoids (Liang et al, 2011, Weinberg et al, 2008 and have previously been shown to decrease placental mRNA levels of 11βHsd2 in mice (Liang et al, 2011). While contradictory to our findings, the mRNAs in the study of Liang et al (2011) were analysed in animals receiving very high doses of alcohol administration (40% EtOH v/v).…”

“…Alcohol crosses the placenta and can directly affect the fetus, or provoke changes in maternal endocrine functions that secondarily can interfere with fetal development and cause metabolic, physiological and endocrine disruptions -or result in miscarriage (Weinberg et al, 2008). Alcohol-induced birth defects may be established before the woman is aware of her pregnancy , therefore women drinking both before pregnancy confirmation and during pregnancy are at risk of delivering a baby with fetal alcohol spectrum disorder (FASD) (Abel, 1999).…”