Novel insights into DNA methylation features in spermatozoa: stability and peculiarities

PLoS One. 2012;7(10):e44479. doi: 10.1371/journal.pone.0044479. Epub 2012 Oct 2.

Abstract

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 and cancer 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CpG Islands
  • DNA Methylation*
  • Databases, Genetic
  • Epigenesis, Genetic
  • Humans
  • Male
  • Middle Aged
  • RNA, Small Untranslated / metabolism
  • Spermatozoa / metabolism*
  • Vocabulary, Controlled

Substances

  • RNA, Small Untranslated

Grants and funding

This work was supported by the European Research Council (ERC) Advanced Grant EPINORC, the Ministerio de Ciencia e Innovación (MICINN) grant SAF2011-22803, the Health Department of the Catalan Government (Generalitat de Catalunya), the Italian Ministry of University (grant PRIN 2010-2012 to CK), the Spanish Ministry of Health (grant FIS -PI11/02254). JS is a “Juan de la Cierva” Researcher. ME is an Institucio Catalana de Recerca i Estudis Avançats (ICREA) Research Professor. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.