Prenatal Alcohol Exposure and Fetal Programming: Effects on Neuroendocrine and Immune Function

Abstract

Alcohol abuse is known to result in clinical abnormalities of endocrine function and neuroendocrine regulation. However, most studies have been conducted on males. Only recently have studies begun to investigate the influence of alcohol on endocrine function in females and, more specifically, endocrine function during pregnancy. Alcohol-induced endocrine imbalances may contribute to the etiology of fetal alcohol syndrome. Alcohol crosses the placenta and can directly affect developing fetal cells and tissues. Alcohol-induced changes in maternal endocrine function can disrupt maternal-fetal hormonal interactions and affect the female's ability to maintain a successful pregnancy, thus indirectly affecting the fetus. In this review, we focus on the adverse effects of prenatal alcohol exposure on neuroendocrine and immune function, with particular emphasis on the hypothalamic-pituitary-adrenal (HPA) axis and the concept of fetal programming. The HPA axis is highly susceptible to programming during fetal development. Early environmental experiences, including exposure to alcohol, can reprogram the HPA axis such that HPA tone is increased throughout life. We present data that demonstrate that maternal alcohol consumption increases HPA activity in both the maternal female and the offspring. Increased exposure to endogenous glucocorticoids throughout the lifespan can alter behavioral and physiologic responsiveness and increase vulnerability to illnesses or disorders later in life. Alterations in immune function may be one of the long-term consequences of fetal HPA programming. We discuss studies that demonstrate the adverse effects of alcohol on immune competence and the increased vulnerability of ethanol-exposed offspring to the immunosuppressive effects of stress. Fetal programming of HPA activity may underlie some of the long-term behavioral, cognitive, and immune deficits that are observed following prenatal alcohol exposure.

Maternal alcohol ingestion reduces surfactant protein A expression by preterm fetal lung epithelia

“…Zhang at al. have demonstrated that alcohol consumption during pregnancy increases Hypothalamic-PituitaryAdrenal (HPA) responsiveness in rat pups in such a way that ethanol-exposed neonates exhibit reduced increase responsiveness in early and pre-weaning life (Zhang et al, 2005). The exact nature and significance of this disturbed hormonal homeostasis still needs to be determined but it is possible that insufficient neonatal corticosteroid levels might be an underlying indicator for inadequate lung surfactant production.…”

Prenatal ethanol exposure disrupts the histological stages of fetal bone development

“…Interestingly, preliminary data indicate that the tibia of fetal guinea pigs prenatally exposed to ethanol also has increased fat content (Keiver and Brien, unpublished data), thereby suggesting that ethanol also alters the balance between adipogenesis and osteogenesis in the fetus. In addition, ethanol intake is known to affect of number of maternal/fetal systems, including the glucocorticoid [40], insulin-like growth factor [3] and calcium-regulating [1,15,16, and 17] systems, all of which could potentially affect bone development.…”

Maternal adrenocorticotropin, cortisol, and thyroid hormone responses to all three-trimester equivalent repeated binge alcohol exposure: ovine model

“…Few studies exist in the human literature on the effects of alcohol consumption on maternal ACTH and cortisol concentrations or on the HPA function of alcohol-exposed children (Zhang et al, 2005). Early human FAS studies on HPA function are based on limited sample size and unreliable self-reporting (Root et al, 1975).…”

“…The prevalence of alcohol consumption among women of child-bearing age remains essentially unchanged despite considerable efforts to educate women about the harmful consequences of alcohol consumption during pregnancy (Caetano et al, 2006;CDC, 2004;Institute of Medicine, 1996;Maternal and Child Health (MCH) Data Report, 2003;NIAAA, 2000) requiring the need to consider other approaches to reduce the negative impact of prenatal alcohol exposure (Cudd, 2005). Numerous hypotheses have been proposed to account for the teratogenic effects of alcohol of which alcohol induced alterations in hypothalamic-pituitaryadrenal (HPA) axis, and hypothalamus-pituitary-thyroid (HPT) axis function are popular (For review, see Zhang et al, 2005).…”