Abstract
Spermiogenesis is a complex cellular differentiation process that the germ cells undergo a distinct morphological change, and the protamines replace the core histones to facilitate chromatin compaction in the sperm head. Recent studies show the essential roles of epigenetic events during the histone-to-protamine transition. Defects in either the replacement or the modification of histones might cause male infertility with azoospermia, oligospermia or teratozoospermia. Here, we summarize recent advances in our knowledge of how epigenetic regulators, such as histone variants, histone modification and their related chromatin remodelers, facilitate the histone-to-protamine transition during spermiogenesis. Understanding the molecular mechanism underlying the modification and replacement of histones during spermiogenesis will enable the identification of epigenetic biomarkers of male infertility, and shed light on potential therapies for these patients in the future.
Highlights
Spermatogenesis is the process of male gamete production with successive cellular differentiation, which can be subdivided into spermatogonial mitosis, spermatocytic meiosis and spermiogenesis (Roosen-Runge, 1962; Hess and Renato De Franca, 2008)
A Th2a-knockout mouse model has yet to be established, mice with knockouts of the testis-specific H2B variants Th2a and Th2b exhibit male infertility with few sperm in the epididymis (Shinagawa et al, 2015). In this double-knockout mouse, impaired chromatin incorporation of transition protein 2 (TP2) and elevated H2B could be observed in the mutant testis, suggesting the TH2A and TH2B may regulate the function in chromatin dynamics or the total histone levels to facilitate the histone replacement during spermatogenesis (Shinagawa et al, 2015)
These results indicate H2A.B might modulate the dynamics of H2AL2 and TP1 chromatin incorporation and removal to participate in the histone-to-protamine transition
Summary
Spermatogenesis is the process of male gamete production with successive cellular differentiation, which can be subdivided into spermatogonial mitosis, spermatocytic meiosis and spermiogenesis (Roosen-Runge, 1962; Hess and Renato De Franca, 2008). SSC (spermatogonial stem cells) undergo self-renewal and differentiate into spermatogonia that perform meiosis to generate haploid germ cells and ensure the genetic diversity through meiotic recombination (Rathke et al, 2014; Bao and Bedford, 2016). The haploid germ cells undergo spermiogenesis with a distinct morphological change and chromatin compaction in the sperm nuclei to prevent the paternal genome from mutagenesis and damage (Govin et al, 2004; Bao and Bedford, 2016). During the nuclear chromatin re-organization in spermiogenesis, the majority of the somatic histones are firstly replaced by testis-specific histone variants, and transition proteins (TPs) are subsequently incorporated in the nuclei of spermatids, protamines (PRMs) further replace TPs in the late spermatids to pack the genome into the highly condensed sperm nucleus (Rathke et al, 2014; Bao and Bedford, 2016). The focus of this review is on recent advances in our knowledge of how epigenetic regulators, such as histone variants, histone modification and their
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