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

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.

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Intersection of Epigenetic and Immune Alterations: Implications for Fetal Alcohol Spectrum Disorder and Mental Health

Frontiers in Neuroscience ◽

10.3389/fnins.2021.788630 ◽

2021 ◽

Vol 15 ◽

Author(s):

Alexandre A. Lussier ◽

Tamara S. Bodnar ◽

Joanne Weinberg

Keyword(s):

Mental Health ◽

Immune System ◽

Immune Function ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Epigenetic Mechanisms ◽

Prenatal Alcohol ◽

Epigenetic Patterns ◽

The Impact

Prenatal alcohol exposure can impact virtually all body systems, resulting in a host of structural, neurocognitive, and behavioral abnormalities. Among the adverse impacts associated with prenatal alcohol exposure are alterations in immune function, including an increased incidence of infections and alterations in immune/neuroimmune parameters that last throughout the life-course. Epigenetic patterns are also highly sensitive to prenatal alcohol exposure, with widespread alcohol-related alterations to epigenetic profiles, including changes in DNA methylation, histone modifications, and miRNA expression. Importantly, epigenetic programs are crucial for immune system development, impacting key processes such as immune cell fate, differentiation, and activation. In addition to their role in development, epigenetic mechanisms are emerging as attractive candidates for the biological embedding of environmental factors on immune function and as mediators between early-life exposures and long-term health. Here, following an overview of the impact of prenatal alcohol exposure on immune function and epigenetic patterns, we discuss the potential role for epigenetic mechanisms in reprogramming of immune function and the consequences for health and development. We highlight a range of both clinical and animal studies to provide insights into the array of immune genes impacted by alcohol-related epigenetic reprogramming. Finally, we discuss potential consequences of alcohol-related reprogramming of immune/neuroimmune functions and their effects on the increased susceptibility to mental health disorders. Overall, the collective findings from animal models and clinical studies highlight a compelling relationship between the immune system and epigenetic pathways. These findings have important implications for our understanding of the biological mechanisms underlying the long-term and multisystem effects of prenatal alcohol exposure, laying the groundwork for possible novel interventions and therapeutic strategies to treat individuals prenatally exposed to alcohol.

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