Impact of nicotine, alcohol, and cocaine exposure on germline integrity and epigenome

Converging evidence suggests that parental exposure to drugs of abuse can affect offspring phenotypes. The impacts of drug abuse on germ cell quality may mediate multigenerational and transgenerational inheritance, although biological pathways underlying this mode of inheritance are not yet characterized. Germline epigenetic marks are modified by drug exposure and have emerged as promising mechanistic candidates in recent work. Drug exposure also impacts overall germline integrity and reproductive functioning, although the role of these consequences in multi/transgenerational inheritance is unclear. This review synthesizes literature on effects of exposure to alcohol, cocaine, and nicotine on the germline with a focus on epigenetic modifications following drug exposure and broader impacts on germline integrity and reproductive functioning. We discuss potential interactions between reproductive functioning, germline integrity, and germline epigenome/transcriptome in pathways underlying multi/transgenerational inheritance. We find that existing data may support independent or interactive contributions of these germline impacts on offspring phenotypes in a manner that may mediate multi/transgenerational inheritance.