Epigenetics of the male gamete

Objective To review and summarize the current understanding of the epigenetic status of human sperm in regards to protamination, specific localization and modifications of retained histones, and DNA methylation. Design Review of the relevant literature. Setting University-based clinical and research laboratories. Patient(s) Fertile and infertile men. Intervention(s) None. Main Outcome Measure(s) Critical review of the literature. Result(s) Sperm from normospermic, fertile men have epigenetic modifications consistent with gene “poising” at the promoters of genes involved in development, including the localization of retained histones with bivalent histone modifications and hypomethylation of DNA. These epigenetic marks are altered in some patients with abnormal spermatogenesis, and in some men who exhibit unexplained, altered embryogenesis during IVF therapy. Conclusion(s) The sperm epigenome implies a poising of the paternal genome for embryogenesis and a possible role in the establishment of totipotency of the embryo and may help in understanding some causes of reduced fertility and transmission of disease risk.