Sperm epigenetic age influences pregnancy outcomes

Estimates highlight that infertility affects about 1 in every five couples seeking children in the United States of America. According to research, about 50% of infertility cases are related to males. The latter is clinically assessed using measures of semen quality set by the World Health Organization. One significant limitation of the standard semen analysis is its poor capacity to predict reproductive success..

Chronological age (age from birth to a given date) is a major fertility determinant. Infertility rates are likely to increase as the parental age at the time of conception has been steadily increasing. Moreover, research has indicated that regardless of maternal age, higher male age contributes to longer time-to-conception, poor pregnancy outcomes, and adverse health results for the offspring at later life stages. While the chronological age partially contributes to these processes, other factors play a role in the equation, like genetics and environmental determinants.

Chronological age significantly influences biological age through an accumulation of epigenetic alterations (a change in the chemical structure of the DNA without affecting the coding sequence), like DNA methylation. Recent advances in research have led to the development of epigenetic clocks—statistical models that allow the identification of biological age in most somatic cells. This allows accurate predictions of the biological age and understanding of how much it deviates from the chronological age. Epigenetic clocks could serve as predictors of cancer incidence, frailty, cardiovascular diseases, and other age-related conditions contributing to longevity. Most of the available research explores the link between epigenetic clocks and somatic cells, while only a few have constructed epigenetic models for male sperms. None of the said studies have discussed the relation between sperm epigenetic clocks and reproductive outcomes. To explore the latter, Pilsner et al. initiated a study on 379 semen samples.

Results revealed that increased sperm epigenetic age (SEA) was associated with a lower probability of achieving pregnancy within 3, 6, and 12 months of trying. The cumulative probability of achieving pregnancy within 12 months was 17% lower for older than younger SEA. A dose-response trend suggested a lower pregnancy probability with increased SEA. Regarding birth outcomes, higher SEA was associated with increased gestational age (a measure of pregnancy age). In addition, smokers were found to have higher SEA numbers.

The researchers concluded that SEA represents a novel biomarker that, along with chronological age, could predict pregnancy success among couples not seeking fertility treatment. Utilizing both biological and chronological ages could provide a better understanding of idiopathic infertility and a chance to predict offspring health.

Source: J Richard Pilsner, Hachem Saddiki, Brian W Whitcomb, Alexander Suvorov, Germaine M Buck Louis, Sunni L Mumford, Enrique F Schisterman, Oladele A Oluwayiose, Laura B Balzer, Sperm epigenetic clock associates with pregnancy outcomes in the general population, Human Reproduction, 2022; https://doi.org/10.1093/humrep/deac084

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