Age-Related Changes in Sperm DNA Methylation and their Forensic and Clinical Implications

Abstract

As a link between a stable genome and a dynamic environment, epigenetics is a promising tool for mapping age-related changes in human DNA. Methylated cytosine changes at specific loci are generally less studied in sperm DNA than in somatic cell DNA. Age-related methylation changes can be connected to various reproductive health problems and multiple disorders in offspring. In addition, they can be helpful in forensic fields, where testing of specific loci in semen samples found at sexual assault crime scenes can predict a perpetrator’s age and narrow down the police investigation. This review focuses on age-related methylation changes in sperm. It covers the biological role of methylation, methylation testing techniques and the implications of methylation changes in forensics and clinical practice.

Plain language summary

DNA methylation is a biological process that can change the activity of a gene without changing its sequence. We do not know much about DNA methylation in sperm and what changes methylation undergoes during the lifespan. These changes can, however, be important both for health and solving crimes. Presperm cells renew themselves, which gives rise to new sperm cells, from youth to death, accumulating cell divisions prone to error. This is why sperm cells are affected by age more than nondividing eggs. Methylation is specific in different tissues of the body. The ratio between number of sperm cells, white blood cells, and other cell types is highly variable and hardly predicted, which may distort the results. Clinical studies have shown that older fathers have worse reproductive health. Their children can develop metabolic, neurological and behavioral disorders. This also applies to younger men whose DNA methylation pattern is similar to that of older men. Methylation changes allow us to build a model capable of predicting the age of an unknown person with a mean error of about 5 years. This can be helpful for police investigators in cases of sexual assault, when biological material is found but there is no match in the police database.

Tweetable abstract

A number of methyl groups on DNA changes with age. In sperm DNA, these changes can influence the successful conception and health of offspring or help police find an unknown criminal offender by predicting their age.

Keywords::

• age prediction
• epigenome
• forensic phenotyping
• methylation
• semen
• sperm

L Kotková contributed to conceptualization, preparing of the original draft, graphics and writing. J Drábek contributed to conceptualization, reviewing, editing and administration. Both authors have read and agreed to the submitted version of the manuscript.

Acknowledgments

Graphics were created with BioRender.com.

Financial disclosure

This work was supported by European Infrastructure for Translational Medicine and funded by LM2023053, CZ.02.1.01/0.0/0.0/16_026/0008448, EF16_013/0001674, LX22NPO5102 and IGA LF UP 2023_006. 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.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with an interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Writing disclosure

The authors thank B Stenglová for help with graphics and J Parrott for proofreading.