| Abstract: | Data about the entire sperm DNA methylome are limited to two sperm donors whereasstudies dealing with a greater number of subjects focused only on a few genes orwere based on low resolution arrays. This implies that information about what wecan consider as a normal sperm DNA methylome and whether it is stable amongdifferent normozoospermic individuals is still missing. The definition of theDNA methylation profile of normozoospermic men, the entity of inter-individualvariability and the epigenetic characterization of quality-fractioned spermsubpopulations in the same subject (intra-individual variability) are relevantfor a better understanding of pathological conditions. We addressed thesequestions by using the high resolution Infinium 450K methylation array andcompared normal sperm DNA methylomes against somatic and cancer cells. Ourstudy, based on the largest number of subjects (n = 8) everconsidered for such a large number of CpGs (n = 487,517),provided clear evidence for i) a highly conserved DNA methylation profile amongnormozoospermic subjects; ii) a stable sperm DNA methylation pattern indifferent quality-fractioned sperm populations of the same individual. Thelatter finding is particularly relevant if we consider that different qualityfractioned sperm subpopulations show differences in their structural features,metabolic and genomic profiles. We demonstrate, for the first time, that DNAmethylation in normozoospermic men remains highly uniform regardless the qualityof sperm subpopulations. In addition, our analysis provided both confirmatoryand novel data concerning the sperm DNA methylome, including its peculiarfeatures in respect to somatic and cancer cells. Our description about a highlypolarized sperm DNA methylation profile, the clearly distinct genomic andfunctional organization of hypo- versus hypermethylated loci as well as theassociation of histone-enriched hypomethylated loci with embryonic development,which we now extended also to hypomethylated piRNAs-linked genes, provides solidbasis for future basic and clinical research. |
