Effects of Moderate Prenatal Alcohol Exposure during Early Gestation in Rats on Inflammation across the Maternal-Fetal-Immune Interface and Later-Life Immune Function in the Offspring

Prenatal exposure to teratogens may alter fetal development and significantly impact later life. Perhaps the best known teratogen is alcohol; prenatal alcohol exposure causes a broad range of effects that can cause lifelong impairment. Of greatest significance are the functional impairments in behavior and cognition. Recognition of these impairments led to the inclusion of the neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders under “conditions for further study.” This proposed diagnosis captures the significant neurodevelopmental and mental health impacts associated with prenatal alcohol exposure and requires impairment in neurocognitive functioning, self-regulation, and adaptive functioning. This chapter reviews clinical impacts of prenatal alcohol exposure, with particular focus on ND-PAE. Methods for comprehensively assessing fetal alcohol spectrum disorders, specifically ND-PAE, are discussed as well as preliminary evidence for implementing effective interventions with these individuals.

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

Experimental Biology and Medicine ◽

10.1177/15353702-0323006-05 ◽

2005 ◽

Vol 230 (6) ◽

pp. 376-388 ◽

Cited By ~ 132

Author(s):

Xingqi Zhang ◽

Joanna H. Sliwowska ◽

Joanne Weinberg

Keyword(s):

Adverse Effects ◽

Immune Function ◽

Hpa Axis ◽

Fetal Programming ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Endocrine Function ◽

Prenatal Alcohol ◽

Induced Changes

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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Association between fetal sex and maternal plasma microRNA responses to prenatal alcohol exposure: evidence from a birth outcome-stratified cohort

Biology of Sex Differences ◽

10.1186/s13293-020-00327-2 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Nihal A. Salem ◽

◽

Amanda H. Mahnke ◽

Alan B. Wells ◽

Alexander M. Tseng ◽

...

Keyword(s):

Statistical Power ◽

Fetal Alcohol Spectrum Disorders ◽

Birth Outcome ◽

Prenatal Alcohol Exposure ◽

Statistical Parameter ◽

Alcohol Exposure ◽

Later Life ◽

Parameter Estimates ◽

Fetal Sex ◽

Prenatal Alcohol

Abstract Most persons with fetal alcohol spectrum disorders (FASDs) remain undiagnosed or are diagnosed in later life. To address the need for earlier diagnosis, we previously assessed miRNAs in the blood plasma of pregnant women who were classified as unexposed to alcohol (UE), heavily exposed with affected infants (HEa), or heavily exposed with apparently unaffected infants (HEua). We reported that maternal miRNAs predicted FASD-related growth and psychomotor deficits in infants. Here, we assessed whether fetal sex influenced alterations in maternal circulating miRNAs following prenatal alcohol exposure (PAE). To overcome the loss of statistical power due to disaggregating maternal samples by fetal sex, we adapted a strategy of iterative bootstrap resampling with replacement to assess the stability of statistical parameter estimates. Bootstrap estimates of parametric and effect size tests identified male and female fetal sex-associated maternal miRNA responses to PAE that were not observed in the aggregated sample. Additionally, we observed, in HEa mothers of female, but not male fetuses, a network of co-secreted miRNAs whose expression was linked to miRNAs encoded on the X-chromosome. Interestingly, the number of significant miRNA correlations for the HEua group mothers with female fetuses was intermediate between HEa and UE mothers at mid-pregnancy, but more similar to UE mothers by the end of pregnancy. Collectively, these data show that fetal sex predicts maternal circulating miRNA adaptations, a critical consideration when adopting maternal miRNAs as diagnostic biomarkers. Moreover, a maternal co-secretion network, predominantly in pregnancies with female fetuses, emerged as an index of risk for adverse birth outcomes due to PAE.

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Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

Perspectives on School-Based Issues ◽

10.1044/sbi13.2.32 ◽

2012 ◽

Vol 13 (2) ◽

pp. 32-42 ◽

Cited By ~ 8

Author(s):

Yvette D. Hyter

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Child Development ◽

Academic Outcomes ◽

Complex Trauma ◽

Prenatal Alcohol Exposure ◽

Alcohol Exposure ◽

Clinical Implications ◽

Prenatal Alcohol ◽

The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

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