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What the human sperm methylome tells us

ABSTRACT: Aim: To characterize the sperm methylome in semen samples from 19 donors with proven fertility. Material and Methods: Bisulfite-converted sperm DNA was hybridized on the HumanMethylation450 Infinium BeadChip platform. CpG fluorescence-intensities were extracted and converted to β-values. Results: The sperm methylome is highly homogeneous and hypomethylated. Genes with hypomethylated promoters are ontologically associated to biological functions related to spermatogenesis and embryogenesis. Sex-chromosomes are the most hypomethylated chromosomes, supporting data that indicated their essential role in spermatogenesis. Ninety-four genes are resistant to demethylation, being strong candidates for transgenerational inheritance. Conclusion: Spermatozoa carry a homogeneous methylation profile that is a footprint of past events (spermatogenesis), is designed to facilitate future events (embryogenesis), and has a possible influence in the adult life (transgenerational effects).

ORGANISM(S): Homo sapiens

PROVIDER: GSE99184 | GEO | 2018/05/01

REPOSITORIES: GEO

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Project description:Data about the entire sperm DNA methylome are limited to two sperm donors whereas studies dealing with a greater number of subjects focused only on a few genes or were based on low resolution arrays. This implies that information about what we can consider as a normal sperm DNA methylome and whether it is stable among different normozoospermic individuals is still missing. The definition of the DNA methylation profile of normozoospermic men, the entity of inter-individual variability and the epigenetic characterization of quality-fractioned sperm subpopulations in the same subject (intra-individual variability) are relevant for a better understanding of pathological conditions. We addressed these questions by using the high resolution Infinium 450K methylation array and compared normal sperm DNA methylomes against somatic cells. Our study, based on the largest number of subjects (n = 8) ever considered for such a large number of CpGs (n = 487,517), provided clear evidence for i) a highly conserved DNA methylation profile among normozoospermic subjects; ii) a stable sperm DNA methylation pattern in different quality-fractioned sperm populations of the same individual. The latter finding is particularly relevant if we consider that different quality fractioned sperm subpopulations show differences in their structural features, metabolic and genomic profiles. We demonstrate, for the first time, that DNA methylation in normozoospermic men remains highly uniform regardless the quality of sperm subpopulations. In addition, our analysis provided both confirmatory and novel data concerning the sperm DNA methylome, including its peculiar features in respect to somatic and cancer cells. Our description about a highly polarized sperm DNA methylation profile, the clearly distinct genomic and functional organization of hypo- versus hypermethylated loci as well as the association of histone-enriched hypomethylated loci with embryonic development, which we now extended also to hypomethylated piRNAs-linked genes, provides solid basis for future basic and clinical research. Bisulphite converted DNA from the 26 normal sperm and 2 somatic cell samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.2

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What the human sperm methylome tells us

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