An Epigenetic Synopsis of Parental Substance Use

Abstract

The rate of substance use is rising, especially among reproductive-age individuals. Emerging evidence suggests that paternal pre-conception and maternal prenatal substance use may alter offspring epigenetic regulation (changes to gene expression without modifying DNA) and outcomes later in life, including neurodevelopment and mental health. However, relatively little is known due to the complexities and limitations of existing studies, making causal interpretations challenging. This review examines the contributions and influence of parental substance use on the gametes and potential transmissibility to the offspring’s epigenome as possible areas to target public health warnings and healthcare provider counseling of individuals or couples in the pre-conception and prenatal periods to ultimately mitigate short- and long-term offspring morbidity and mortality.

Plain language summary

More people, especially those of reproductive age, are using substances, and there is growing evidence to suggest that parental substance use before and during pregnancy may adversely affect offspring and result in issues later in life, including mental health challenges. Such relationships have been demonstrated with nicotine, alcohol, cannabis, opioids and illegal drugs (e.g., heroin, cocaine, methamphetamines). Some of these adverse impacts on offspring can potentially be passed down in families even after parents have quit using the substance. Because more individuals are using drugs, especially during the COVID-19 pandemic, it is important that families learn more about the potential impact of substance use on their future offspring before they try to get pregnant.

Tweetable abstract

Substance use before and during pregnancy can influence the offspring epigenome and later health outcomes. This is an area to target in public healthcare warnings and healthcare provider counseling to ultimately mitigate offspring morbidity and mortality.

Keywords::

• DNA methylation
• epigenetic inheritance
• histone modifications
• intergenerational epigenetic inheritance
• maternal drug use
• paternal drug use
• preconception drug use
• prenatal drug use
• transgenerational epigenetic inheritance

Author contributions

J Lo: conceptualization, investigation, writing (original draft; review and editing). R D’Mello: investigation, writing (original draft; review and editing). L Watch: investigation, writing (original draft; review and editing). D Schust: investigation, writing (original draft; review and editing). S Murphy: conceptualization, investigation, writing (original draft; review and editing).

Financial & competing interests disclosure

The authors received grant support from the National Institutes of Health (DP1 DA056493) and the John Templeton Foundation (60957). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors received grant support from the National Institutes of Health (DP1 DA056493) and the John Templeton Foundation (60957). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.