Epidemiological studies in humans suggest that acquired paternal traits, such as obesity, are associated with a higher risk of fathering small for gestational age offspring. Studies in non-human mammals suggest that such associations could be mediated by DNA methylation changes in spermatozoa that influence offspring development in utero. Human obesity is associated with differential DNA methylation in peripheral blood. It is unclear, however, whether this differential DNA methylation is reflected in less readily available tissues such as spermatozoa. In this study, we profiled genome-wide DNA methylation with the Infinium MethylationEPIC array in matched samples of human blood and sperm from lean (discovery n = 47; replication n = 21) and obese (n = 22) healthy males of proven fertility. To characterize sperm-specific DNA methylation signatures, we compared spermatozoal DNA methylation data to that of nearly 6,000 somatic tissue samples available on the Gene Expression Omnibus database. We studied covariation patterns between whole blood and sperm and investigated consistent obesity-associated DNA methylation differences.
Overall design
Matched whole blood and sperm DNA methylation samples were collected from 47 lean, healthy men. Two replication cohorts included matched whole blood and sperm DNA methylation samples from 21 lean men and 22 obese men, respectively. The samples were analyzed for differences in DNA methylation between whole blood and sperm (paired t-test), covariation between the two tissues (Pearson's correlation test) and obesity associations (linear models in each of the tissues; linear mixed effects model across both tissues and all three cohorts)
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