Epigenetic markers in the embryonal germ cell development and spermatogenesis

Abstract

Spermatogenesis is the process of generation of male reproductive cells from spermatogonial stem cells in the seminiferous epithelium of the testis. During spermatogenesis, key spermatogenic events such as stem cell self-renewal and commitment to meiosis, meiotic recombination, meiotic sex chromosome inactivation, followed by cellular and chromatin remodeling of elongating spermatids occur, leading to sperm cell production. All the mentioned events are at least partially controlled by the epigenetic modifications of DNA and histones. Additionally, during embryonal development in primordial germ cells, global epigenetic reprogramming of DNA occurs. In this review, we summarized the most important epigenetic modifications in the particular stages of germ cell development, in DNA and histone proteins, starting from primordial germ cells, during embryonal development, and ending with histone-to-protamine transition during spermiogenesis.

Keywords: DNA methylation; Fertilization; Histone acetylation; Histone methylation; Sperm epigenetics; Spermatogenesis; Spermatozoa.

Fig. 1

Three main groups of epigenetic modifications observed in mammalian cells. rRNA – ribosomal RNA, tRNA – transfer RNA, siRNA – silencer RNA, miRNA – micro RNA, snRNA – small nuclear RNA, snoRNA – small nucleolar RNA, piRNA – piwi-interacting RNA, lncRNA – long non-coding RNA, ADP – adenosine diphosphate, SUMO – small ubiquitin-like modifier

Fig. 2

Global DNA methylation changes during human embryonal development. Dashed line means the estimated (but still unknown) time points of the remethylation phase in arrested gonocytes. The full methylation pattern is established either until birth or before puberty, and is sustained to the end of spermatogenesis. Dots represent the most important steps of DNA methylation. PGCs – primordial germ cells, SSCs – spermatogonial stem cells

Fig. 3

The most important histone post-translational modifications at particular stages of human spermatogenesis. a The main histone post-translational modifications during embryonal development, mitotic proliferation, and spermiogenesis, together with indication of the cell type, their ploidy and morphology. b The main histone post-translational modifications during prophase I (the most important stage of first meiotic division in primary spermatocytes). Epigenetic modifications found on autosomal chromosomes are marked in black, while modifications representative for sex chromosomes are marked in blue. PGCs – primordial germ cells, SSCs – spermatogonial stem cells, SPC – spermatocyte, SPD – spermatid, ac – acetylation, me – methylation, ph – phosphorylation, ub – ubiquitination, 1n – haploid genome, 2n – diploid genome, 4n – tetraploid genome

Fig. 4

Main variants of the histones during the spermatogenetic process (human and mice)