Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics

Abstract

Haploid male germ cells package their DNA into a volume that is typically 10% or less that of a somatic cell nucleus. To achieve this remarkable level of compaction, spermatozoa replace most of their histones with smaller, highly basic arginine and (in eutherians) cysteine rich protamines. One reason for such a high level of compaction is that it may help optimise nuclear shape and hence support the gametes' swimming ability for the long journey across the female reproductive tract to the oocyte. Super-compaction of the genome may confer additional protection from the effects of genotoxic factors. However, many species including the human retain a fraction of their chromatin in the more relaxed nucleosomal configuration that appears to run counter to the ergonomic, toroidal and repackaging of sperm DNA. Recent research suggests that the composition of this 'residual' nucleosomal compartment, a generally overlooked feature of the male gamete, is far more significant and important than previously thought. In this respect, the transport and incorporation of modified paternal histones by the spermatozoon to the zygote has been demonstrated and indicates another potential paternal effect in the epigenetic reprogramming of the zygote following fertilisation that is independent of imprinting status. In this review, the most recent research into mammalian spermatozoal chromatin composition is discussed alongside evidence for conserved, non-randomly located nucleosomal domains in spermatozoal nuclei, all supporting the hypothesis that the spermatozoon delivers a novel epigenetic signature to the egg that may be crucial for normal development. We also provide some thoughts on why this signature may be required in early embryogenesis.

Paternal contribution to development: Sperm genetic damage and repair in fish

“…Sperm DNA methylation pattern is close to that observed in embryonic stem cells, showing hypomethylation at developmental promoters (Hammoud et al 2009;Schagdarsurengin et al 2012). After fertilization, sperm DNA is quickly demethylated in mammals except in some specific loci (O'Doherty and McGettigan 2014;Miller et al 2010;Okada et al 2010) which are supposed to be necessary for a proper progress in early embryogenesis. However in zebrafish, whose sperm chromatin, as was explained before, is fully compacted with histones (Wu et al 2011), DNA reprogramming after fertilization follows a different mechanism, early embryos inheriting sperm DNA methylome (Jiang et al 2013).…”

“…Since the first attempts to decipher the RNA profile of human spermatozoa (Miller et al 2010;Kumar et al 1993;Miller et al 1999;Pessot et al 1989), technologies have evolved to high throughput ones which have facilitated to a large extent the analysis of spermatozoa RNA profiles.…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…It is a critical step in gamete development, and the compacted structure of the chromatin transmits vital information to the embryo to guide it through development. The lack of proper DNA packaging in sperm has been associated with infertility in mice [160]. During the chromatin re-packaging in spermatogenesis process, about 85 % of the histones are replaced by protamines [161].…”

Direct and delayed X‐ray‐induced DNA damage in male mouse germ cells

“…Spermatocytes undergo a long prophase and two meiotic divisions to give rise to haploid spermatids, which then mature into motile spermatozoa. During this last phase, chromatin is extensively remodeled, and somatic histones are replaced with basic transition proteins followed by protamines that condense the chromatin [Miller et al, 2010;Ward, 2010]. This process requires the introduction of DNA strand breaks to eliminate negative supercoiling.…”