Inheritance of paternal lifestyles and exposures through sperm DNA methylation

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. 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.

Automated summary

The authors investigate the impact of environmentally driven changes in the sperm epigenome on offspring health and discuss the use of human stem cell models to study the paternal origins of health and disease. Various lifestyle factors and environmental chemicals pose a threat to human reproductive health. Parental preconception exposure can lead to alterations in gametes, which may negatively affect embryo growth and development. While the connection between maternal exposures and offspring health is frequently studied, the importance of paternal preconception exposures is often overlooked. Innovations in human stem cell-based spermatogenic models can provide insights into the paternal determinants of offspring health and disease.