Sperm epigenetic aging may help predict pregnancy success

US researchers have found that sperm epigenetic aging — the biological, rather than chronological, aging of sperm — has the potential to predict the success and time it takes to become pregnant. Their findings, published in the journal Human Reproduction, underscore the importance of the male partner in reproductive success.

“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 Dr J Richard Pilsner from Wayne State University, lead author of the study.

“Semen quality outcomes utilising World Health Organization guidelines have been used to assess male infertility for decades, but they remain poor predictors of reproductive outcomes. Thus, 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.”

The researchers studied 379 male partners of couples who discontinued the use of contraception for the purpose of becoming pregnant. The study found a 17% lower cumulative probability of pregnancy after 12 months for couples with male partners in older compared to younger sperm epigenetic aging categories. The study also found a higher epigenetic aging of sperm in men who smoked.

The results, Pilsner said, indicate that higher sperm epigenetic aging is associated with a longer time to become pregnant in couples not assisted by fertility treatment, and with shorter gestation among those couples that achieved pregnancy.

The strong association between sperm epigenetic aging and pregnancy probability and its slowing or reversal through lifestyle choices and/or pharmacological interventions, warrants further investigation, the researchers say. In addition, because older fathers have an increased risk of children with adverse neurological outcomes, it is important to understand the potential relation of sperm epigenetic aging on children’s health and development.

“There is a critical need for new measures of male fecundity for assessing overall reproductive success among couples in the general population,” Pilsner said. “These data show that our sperm epigenetic clocks may fulfil this need as a novel biomarker that predicts pregnancy success among couples not seeking fertility treatment.

“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. Such a summary measure of sperm biological age is of clinical importance, as it allows couples in the general population to realise their probability of achieving pregnancy during natural intercourse, thereby informing and expediting potential infertility treatment decisions.”

Image credit: ©stock.adobe.com/au/Christoph Burgstedt

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