Developmental impairments induced by prenatal exposure to substance abuse

Imagine a world where each living individual upholds the secrets of past generations. This world is not a pop up from a fiction novel, but rather the reality of many organisms whose genetic expression is orchestrated and fine tuned by an epigenetic machinery. Recent scientific breakthroughs have discouraged the traditional belief that the epigenome is of a stagnant nature, and have thus progressed the idea that the machinery’s multiple modifications are dynamic as well as susceptible to environmental outcomes. 

The human epigenome is particularly sensitive to secondary, nonnormative environmental factors such as early exposure to psychoactive substances (alcohol, smoke, tobacco, cocaine, etc.)  that can drive epigenetic changes in gametes, consequently prolonging the effects of the exposure beyond the current generation and into future, unexposed generations. The most profound influence on epigenetic states occurs during prenatal life, more specifically during gametogenesis and embryogenesis, where progressive waves of genome-wide demethylation and re-methylation increase genetic/environmental stimuli vulnerability and result in the potential acquirement or deletion of epigenetic markings that can stimulate both short or long term effects on fetal programming via mechanisms of epigenetic memory. Substance abuse during pregnancy interferes with the normal epigenetic machinery, triggering a series of impairments in crucial environmental inputs of fetal programming such as the placenta, uterine tissue, offspring-mother hormonal balance, and proper maternal blood supply. 

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Alcohol exposure can severely impair human physical and neurobehavioral development with the obstruction of epigenetic markings potentially directing organ development, hormonal balance, and normal metabolic development. Prenatal exposure to alcohol has also been linked to aberrant genetic expression induced by alterations in genes controlling methylation, chromatin remodeling and protein synthesis, including histone hyperacetylation, hypermethylation in genes controlling metabolic pathways, and hypomethylation in genes associated with development, genomic imprinting and chromatin remodeling. Nicotine intake has been associated with pulmonary malformation and metabolic syndromes such as obesity, high blood pressure, and altered glucose homeostasis including a resistance to insulin both in the first and second generation offspring. Prenatal tobacco exposure can potentially influence global and gene-specific DNA methylation by targeting imprints in males. Smoking is also believed to alter brain plasticity and proper neurological development through promoter methylation in genes crucial for brain development such as BDNF, and has further been linked to neurotransmitter impairment in the fetal heart. Cannabis is also believed to cause neurotransmitter impairment, specifically by decreasing the expression of DRD2 (dopamine receptor D2) mRNA in the brain, increasing addiction vulnerability in the growing fetus. On the other hand, exposure to illicit drugs such as cocaine, heroin and amphetamine has of late been associated with the development of malignant neoplasms and heart dysfunction leading to shorter lifespans. 

Although DNA methylation remains the most studied epigenetic mechanism underlying substance-exposure diseases, it is by no means the sole contributor. Substance abuse has shown to trigger multiple epigenetic pathways, with most inducing an overall gene downregulation. Therefore, determining which epigenetic regulators are vital participants and stressors in prenatal development would help improve pregnancy outcomes via the potential control of diseases and undesirable complications.

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Bibliography 

Vaiserman, A. M. (2013). Long-term health consequences of early-life exposure to substance abuse: an epigenetic perspective. Journal of Developmental Origins of Health and Disease, 4(4), 269–279. doi:10.1017/S2040174413000123