Epigenetic effects of psychoactive substance use on male germ cells and its implication for the neurodevelopment of offspring: A narrative review
DOI:
https://doi.org/10.62954/n7ckx122Keywords:
Epigenetics, Spermatozoa, Neurodevelopment, Psychoactive SubstancesAbstract
The consumption of psychoactive substances has been negatively associated with male fertility, compromising not only semen quality but also the genetic and epigenetic integrity of spermatozoa; these alterations may have significant implications for the neurodevelopment of the offspring. Current evidence indicates that substances such as alcohol, tobacco/nicotine, cannabis, and cocaine induce changes in DNA methylation, histone modification, and disruption of non-coding RNAs in male germ cells. The aim of this review was to analyze how epigenetic changes induced by paternal preconception exposure to psychoactive substances may affect the brain development of the offspring. To achieve this, an integrative narrative review was conducted through a search of scientific literature in various databases, including English-language articles published between 2020 and 2025, selected based on their relevance in the fields of epigenetics and reproduction. The findings indicate that such epigenetic modifications in sperm impact key genes, including BDNF, DLGAP2, Cdkn1a, and Shank1, which are involved in synaptic plasticity, the hypothalamic-pituitary-adrenal axis, dopaminergic function, and an increased risk of autism. In animal models, these alterations persist in the brains of the offspring, manifesting as behavioral disorders, attention deficits, and reduced drug sensitivity. This evidence suggests the role of sperm exposed to psychoactive substances in transmitting epigenetic marks to the next generation, affecting brain programming and increasing the risk of neurodevelopmental disorders.
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