Associations of sperm epigenetic aging with semen parameters among men from the US general population

Abstract Study question Is sperm epigenetic aging (SEA) associated with semen parameters among men in the general population? Summary answer While SEA was not associated with general semen parameters, advanced SEA was positively associated with sperm head defects such as length, perimeter, and pyriforms. What is known already We have previously shown that advanced SEA was strongly associated with longer time-to-pregnancy among couples in the general population. Study design, size, duration A population-based prospective cohort study of couples discontinuing contraception to become pregnant recruited from 16 US counties from 2005 to 2009. Participants/materials, setting, methods Sperm DNA methylation from 379 semen samples were assessed via Illumina EPIC Array and SEA was estimated using Super Learner, an ensemble machine learning algorithm. Linear regression models were employed to examine the associations between semen parameters and SEA adjusting for male age and current smoking. Main results and the role of chance None of the general semen characteristics such as count, concentration, motility or morphology were associated with SEA. However, several sperm head parameters were positively associated with SEA including length (β = 3.6, 95% confidence internal (CI): 1.01 - 6.23; p = 0.007); perimeter (β = 4.04, 95% CI: 0.1 – 0.05; p = 0.045) and pyriforms (β = 0.29, 95% CI: 0.1-0.49; p = 0.003). SEA was also inversely related to sperm elongation factor (β = -2.9, 95% CI: -4.8 - -1.1; p = 0.002). Limitations, reasons for caution This prospective cohort study consisted primarily of Caucasian men and women and thus large diverse cohorts are necessary to confirm the associations between SEA and sperm head defects in other races/ethnicities. Wider implications of the findings These data suggest that advanced sperm epigenetic aging may be related to improper sperm head condensation during spermatogenesis. Trial registration number N/A