Alcohol-Induced Developmental Origins of Adult-Onset Diseases

Abstract

Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD.

Maternal alcohol consumption during pregnancy and its association with offspring renal function at 30 years: Observation from a birth cohort study

“…On the other hand, there might be overlapping influences between several polygenic, epigenetic, and environmental factors in developmental paths that engender both malformations and organ malfunction resulting in disease during adulthood . All this follows the framework first outlined by David Barker hypothesis on developmental origins of health and disease . Prenatal exposure to alcohol is adversely associated with cardiovascular, neurological deficits, endocrine dysfunction, and nutrient homeostasis.…”

“…There is also an association with high carotid‐femoral pulse wave velocity, which in turn predicts cardiovascular morbidity and mortality at adulthood, as reported in another Australian longitudinal study . Such exposure also correlates with endocrine dysfunction and nutrient homeostasis instability . However, prenatal exposure to alcohol and its long‐term effect on renal function remains poorly documented.…”

Alcohol consumption in a general antenatal population and child neurodevelopment at 2 years

“…In addition, knowledge of genotypes related to alcohol metabolism is yielding important information about cognitive development in children following PAE,55 as is a growing understanding of epigenetic markers in the fetus,56 and in paternal sperm,57 that alter developmental programming. Research in these areas is in its infancy but likely to yield novel and important information in the near future as advances in genomic technology allow for more detailed investigations into the risk of having a child with FASD.…”

DNA modifications in models of alcohol use disorders

“…Alcohol exposure can cause widespread perturbations to methylation programming (Zhou, Chen, & Love, 2011a) and improper cell differentiation (Zhou et al, 2011b), which can contribute to developmental disorders and neurobehavioral deficits that can persist into adulthood (reviewed in Lunde et al, 2016). Prenatal ethanol exposure increases adult mouse hippocampal expression of Slc17a6 , which encodes the VGLUT2 protein and is associated with hypomethylation of that gene’s promoter, though it is worth noting that VGLUT2 protein expression was decreased (Zhang, Ho, Vega, Burne, & Chong, 2015).…”

“…Despite an increasing interest in epigenetic inheritance research, the exact mechanisms of these transgenerational phenomena remain unclear (Heard & Martienssen, 2014). The majority of other research into FASD is beyond the scope of this review, but has been reviewed elsewhere (see Liyanage et al, 2014;; Lunde et al, 2016;; Basavarajappa & Subbanna, 2016). …”