One plausible mechanism for the environment to alter cancer susceptibility is through DNA methylation. Alterations in DNA methylation can lead to genomic instability and altered gene transcription. Genomic DNA methylation levels have been inversely associated with age suggesting that factors throughout life may be associated with declines in DNA methylation. Using information from a multi-ethnic New York City birth cohort (born between 1959 and 1963), we examined whether genomic DNA methylation, measured in peripheral blood mononuclear cells, was associated with smoking exposure and other epidemiologic risk factors across the lifecourse. Information on prenatal and childhood exposures was collected prospectively through 1971; and information on adult exposures and blood specimens were collected in adulthood from 2001-2007. Methylation levels of leukocyte DNA were determined using a [3H]-methyl acceptance assay where higher values of DPM/μg DNA indicate less DNA methylation. Genomic methylation of leukocyte DNA differed by ethnicity (66% of blacks, 48% of whites, and 29% of Hispanics were above the median level of DPM/μg DNA) (p = 0.03). In multivariable modeling, DNA methylation was statistically significantly associated with maternal smoking during pregnancy, longer birth length, later age at menarche, nulliparity, and later age at first birth. These data, if replicated in larger samples, suggest that risk factors across the lifecourse may be associated with DNA methylation in adulthood. Larger studies and studies that measure within-individual changes in DNA methylation over time are a necessary next step.
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
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