Evaluating the Epigenetic Age of Sperm to Predict Pregnancy Outcomes

Women’s health behaviors and age have historically been seen as the determining factors to a successful pregnancy. Of course, that view has been changing over the years as more research examines the male partner’s role in fertility.

One factor considered significant to males’ reproductive capability is their age. Generally, that means taking into account their chronological age. But chronological age doesn’t accurately depict the “true age” of a person…or, in the case of fertility, the biological age of a male’s reproductive cells.

To accurately assess sperm age and its significance for an effective pregnancy outcome, researchers from Wayne State University (WSU) School of Medicine in Michigan sought to evaluate sperm using an epigenetic aging clock. Their results, presented in the journal Human Reproduction, revealed that epigenetic age might be a useful biomarker in predicting a couple’s time to pregnancy.  

“Chronological age is a significant determinant of reproductive capacity and success among couples attempting pregnancy, but chronological age does not encapsulate the cumulative genetic and external – environmental conditions – factors, and thus it serves as a proxy measure of the ‘true’ biological age of cells,” said lead author, J. Richard Pilsner, Ph.D., Professor and Robert J. Sokol, MD Endowed Chair of Molecular Obstetrics and Gynecology at WSU.

Pilsner also added that the World Health Organization’s guidelines for assessing male infertility have not been very good at predicting pregnancy outcomes. He said, “The ability to capture the biological age of sperm may provide a novel platform to better assess the male contribution to reproductive success, especially among infertile couples.”

Epigenetic clocks primarily measure DNA methylation, which is the addition of a methyl group to DNA. As a person ages, these methyl marks can accumulate on certain regions of the genome and are affected by a person’s environment and experiences. Hence, accelerated aging has been associated with many conditions like heart disease, cancer, and obesity, as well as early mortality.

Prior studies have found that epigenetic factors play an important role in sperm development. Because spermatogenesis occurs daily, the epigenome of sperm is highly sensitive to an individual’s environmental exposure and metabolic state. Adverse conditions can negatively affect sperm quality and count, leading to male infertility.

In the current study, the researchers analyzed the sperm epigenetic age (SEA) of 379 males who, together with their female partners, discontinued contraception in order to get pregnant. What they found was that couples with older SEA male partners had a 17% lower chance of getting pregnant after one year compared to couples with younger SEA male partners.  

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The study also noted that men who smoked had higher SEA. This point correlates to other articles we have reviewed in WIE, such as how using nicotine, as well as marijuana, can cause epigenetic changes in the testes that compromise fertility.

According to Dr. Pilsner, the overall results show that higher SEA is associated with a longer time to getting pregnant naturally and with shorter gestational age after achieving pregnancy with or without fertility assistance.

Additional research is needed to verify the results here, especially considering the limitations in size and diversity of the participants. However, because epigenetic modifications are potentially reversible, further studies on whether SEA can be reversed or slowed down with lifestyle choices or medicine should also be considered and would greatly benefit fertility assistance measures.

It’s known that the older the father is at conception, the more a child’s chances of developing a neurological disorder. Therefore, understanding the potential risks of SEA in pregnancy and how it impacts a child’s future health and development is essential for those seeking a natural pregnancy or for those pursuing fertility assistance, like IFV.

“While chronological age of both partners remains a significant predictor of reproductive success, our clocks likely recapitulate both external and internal factors that drive the biological aging of sperm,” said Dr. Pilsner. “Such a summary measure of sperm biological age is of clinical importance, as it allows couples in the general population to realize their probability of achieving pregnancy during natural intercourse, thereby informing and expediting potential infertility treatment decisions.”

Source: J Richard Pilsner, et al. Sperm epigenetic clock associates with pregnancy outcomes in the general populationHuman Reproduction, May 2022

Reference: New measure of sperm age may be predictor of pregnancy success. Wayne State University – Office of the Vice President for Research. May 13, 2022.

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