Paternal Age-Associated Genetic and Epigenetic Changes and Neurodevelopmental Disorders

September 19, 2022

Chemical Exposures and Lifestyle Factors May Affect the Normal Process of Epigenetic Aging of Sperm

Delayed parenthood is a common feature of many developed countries. Unfortunately, this delay comes with consequences. Older couples in the pursuit of having biological children are generally less fertile, and often there are concerns about the health and development of their future offspring. In situations like these, clinicians tend to be primarily concerned with advanced maternal age. In contrast, the influence of paternal age on fertility, early development, and the child’s health is rarely acknowledged. It is due to this reason that a group of researchers produced a review article that examines advanced paternal age. Specifically, the review investigated studies that reported age-associated epigenetic changes in mammal and human sperm, including DNA methylation, histone modifications, and non-coding RNAs. Disappointingly, the research team found these changes poorly understood within the reviewed medical literature. For instance, some human and rodent studies suggest that most sperm age-dependent differentially methylated regions (aDMRs) undergo hypermethylation with age, whereas other studies did not. Also discovered is that various animal studies indicate that the rate of DNA methylation changes over the lifespan is not uniform, and significant modifications mainly occur during puberty. But, the successful development of the human sperm epigenetic clock indicates that at least some aDMRs have a direct relationship between methylation levels and paternal age. Some rodent studies which analyzed age-dependent DNA methylation showed that age-dependent epigenetic mechanisms target the same genes and biological functions. Additionally, most human and animal studies identified a similar list of biological categories enriched by age-dependent epigenetic mechanisms in sperm, including embryonic developmental, neurodevelopmental, growth, and metabolic pathways. Therefore, the researchers suggest that age-dependent changes in the sperm epigenome cannot be described by the random accumulation of epimutations. The review concludes that an emerging body of studies indicates that chemical exposures and lifestyle factors may affect the normal process of epigenetic aging of sperm. 

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