The epigenome of the postnatal male germline: A double-edged sword between flexibility and stability

Abstract Epigenetic regulation is central to cell development and functions in multicellular organisms. In the male gonads of mice, it contributes to the control of spermatogenesis, the process of spermatozoa production by differentiation of spermatogonial stem cells (SSCs) and subsequent spermatogenic cells. As male germ cells progress through spermatogenesis, their transcriptional activity changes dynamically to enable the transition from mitotically dividing SSCs to meiotic spermatocytes, and morphological changes necessary to generate spermatozoa. An ensemble of fine-tuned epigenetic factors and mechanisms regulates transcriptional activity. Their disruption can result in sub- or infertility. This review discusses recent advances in epigenetic regulation in the postnatal male germline from SSCs formation and differentiation to mitosis-to-meiosis transition and post-meiotic maturation. It describes the processes of plasticity of the germline epigenome and how some epigenetic marks are stably maintained in spermatozoa and can in some cases, be passed to the embryo and influence offspring phenotypes. The review outlines open questions about the way these processes are coordinated across developmental stages and their biological importance.