The sperm nucleus: chromatin, RNA, and the nuclear matrix

Abstract

Within the sperm nucleus the paternal genome remains functionally inert and protected following protamination. This is marked by a structural morphogenesis that is heralded by a striking reduction in nuclear volume. Despite these changes, both human and mouse spermatozoa maintain low levels of nucleosomes that appear non-randomly distributed throughout the genome. These regions may be necessary for organizing higher order genomic structure through interactions with the nuclear matrix. The promoters of this transcriptionally quiescent genome are differentially marked by modified histones that may poise downstream epigenetic effects. This notion is supported by increasing evidence that the embryo inherits these differing levels of chromatin organization. In concert with the suite of RNAs retained in the mature sperm they may synergistically interact to direct early embryonic gene expression. Irrespective, these features reflect the transcriptional history of spermatogenic differentiation. As such they may soon be utilized as clinical markers of male fertility. In this review we explore and discuss how this may be orchestrated.

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

“…Spermatozoa possess a considerable store of RNA particles in spite of its transcriptional inactivity and the lack of rRNA (Johnson et al 2011;Miller et al 2005) that excludes the translation process in the sperm cell (Miller et al 2005;Jodar et al 2013). During spermatogenesis, a constant transcription activity exists until the spermatid formation; then, cytoplasm and RNA content are reduced gradually to the residual or chromatoid body.…”

“…During spermatogenesis, a constant transcription activity exists until the spermatid formation; then, cytoplasm and RNA content are reduced gradually to the residual or chromatoid body. The original explanation for the presence of RNA in the spermatozoa was attributed to an incomplete removal of cytoplasmic RNA during spermiogenesis but recent data suggest a selective retention of particular transcripts (Johnson et al 2011;Miller et al 2005;Hamatani 2012;Hosken and Hodgson 2014). Spermatic RNAs are coded by the diploid genome, being equivalent in all the spermatozoa from the ejaculate, independently of the particular haplotype of each spermatozoon (Hosken and Hodgson 2014).…”

“…This study confirmed a sperm-specific mRNA profile which included transcripts with a potential role in fertilization and development. Several reports suggest that the retention of mRNAs in mature sperm is species specific, revealing that they are released into the oocyte and maintained in the zygote (Johnson et al 2011;Hamatani 2012;Avendano et al 2009;Ostermeier et al 2004). Transcriptome of zebrafish was analyzed by Wu and colleagues (Wu et al 2011), who identified that the most enriched transcripts are from 1731 genes (encoding ribosomal proteins, actin, tubulin, etc), corresponding to genes showing histone activating marks and DNA hypomethylation in sperm chromatin.…”

Epigenetic Inheritance of Disease and Disease Risk

“…Similarly, not all histones in sperm are replaced by protamines and those that are maintained likely keep their PTMs and can be transferred to the oocyte (Hammoud et al, 2009;Brykczynska et al, 2010). Further to DNAme and HPTMs, new data also point to a role for noncoding RNAs in the transgenerational information transfer through the germline (Johnson et al, 2011a). Together, these findings provide potential mechanistic pathways possibly underlying germline transmission of epigenetic marks.…”

“…However, it has been known for several decades that a sizable proportion of histones are retained in sperm cells (Gusse et al, 1986;Gatewood et al, 1990). Although this proportion is modest in mice (1-2%), in humans an estimated 4-15% of histones are retained (Hammoud et al, 2009;Johnson et al, 2011a). Only recently has it been demonstrated, however, that HPTMs can also be maintained in the sperm and transferred to the oocyte where they likely play a critical role in embryonic development after fertilization (Hammoud et al, 2009;Brykczynska et al, 2010).…”