Inheritance of paternal lifestyles and exposures through sperm DNA methylation

• Published in: Nature reviews. Urology Vol. 20; no. 6; pp. 356 - 370
• Main Authors: Greeson, Katherine W., Crow, Krista M. S., Edenfield, R. Clayton, Easley, Charles A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2023; Nature Publishing Group
• Subjects: 631/136/2434/1822; 631/208/176/1988; 631/532; DNA methylation; Epigenetics; Medicine; Medicine & Public Health; Review Article; Sperm; Stem cells; Urology
• ISSN: 1759-4812; 1759-4820
• DOI: 10.1038/s41585-022-00708-9

Many different lifestyle factors and chemicals present in the environment are a threat to the reproductive tracts of humans. The potential for parental preconception exposure to alter gametes and for these alterations to be passed on to offspring and negatively affect embryo growth and development is of concern. The connection between maternal exposures and offspring health is a frequent focus in epidemiological studies, but paternal preconception exposures are much less frequently considered and are also very important determinants of offspring health. Several environmental and lifestyle factors in men have been found to alter sperm epigenetics, which can regulate gene expression during early embryonic development. Epigenetic information is thought to be a mechanism that evolved for organisms to pass on information about their lived experiences to offspring. DNA methylation is a well-studied epigenetic regulator that is sensitive to environmental exposures in somatic cells and sperm. The continuous production of sperm from spermatogonial stem cells throughout a man’s adult life and the presence of spermatogonial stem cells outside of the blood–testis barrier makes them susceptible to environmental insults. Furthermore, altered sperm DNA methylation patterns can be maintained throughout development and ultimately result in impairments, which could predispose offspring to disease. Innovations in human stem cell-based spermatogenic models can be used to elucidate the paternal origins of health and disease. Here, the authors explore how environmentally driven changes in the sperm epigenome can mediate paternal contributions to offspring health. They also describe innovations in human stem cell models that can be used to elucidate the paternal origins of health and disease. Key points A number of lifestyle factors and environmental exposures can alter the epigenome in gametes, which can contribute to the development of disease in offspring. Maternal exposures have been heavily investigated with respect to their influence on offspring, but paternal exposures have been largely overlooked. Paternal exposures are important to explore as they often reflect maternal exposures and sperm are continuously produced throughout adult life from a stem cell pool located outside the blood–testis barrier. Human stem cell-based methods might improve understanding of the influence of paternal exposures on offspring health and development without the challenges of species differences and confounding maternal exposures.