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.

During the haploid phase of mammalian spermatogenesis, nucleosomal chromatin is ultimately repackaged by small, highly basic protamines to generate an extremely compact, toroidal chromatin architecture that is critical to normal spermatozoal function. In common with several species, however, the human spermatozoon retains a small proportion of its chromatin packaged in nucleosomes. As nucleosomal chromatin in spermatozoa is structurally more open than protamine-packaged chromatin, we considered it likely to be more accessible to exogenously applied endonucleases. Accordingly, we have used this premise to identify a population of endonuclease-sensitive DNA sequences in human and murine spermatozoa. Our results show unequivocally that, in contrast to the endonuclease-resistant sperm chromatin packaged by protamines, regions of increased endonuclease sensitivity are closely associated with gene regulatory regions, including many promoter sequences and sequences recognized by CCCTC-binding factor (CTCF). Similar differential packaging of promoters is observed in the spermatozoal chromatin of both mouse and man. These observations imply the existence of epigenetic marks that distinguish gene regulatory regions in male germ cells and prevent their repackaging by protamines during spermiogenesis. The ontology of genes under the control of endonuclease-sensitive regulatory regions implies a role for this phenomenon in subsequent embryonic development.

A challenge in the field of ecotoxicology is the linkage of alterations at molecular and biochemical levels of organization to adverse outcomes in individuals and populations. In the present study, a predictive relationship between plasma vitellogenin (VTG) concentration and fecundity in female fathead minnows (Pimephales promelas) was derived from 21‐d laboratory toxicity tests with five chemicals (17β‐trenbolone, 17α‐trenbolone, prochloraz, fenarimol, and fadrozole) that inhibit VTG production through different mechanisms. Because VTG is key to egg production in female oviparous animals, changes in the lipoprotein could, theoretically, serve as an indicator of reproductive success. Regression of fecundity versus VTG concentration from the various studies yielded a highly significant linear model (fecundity = −0.042 + 0.95‐VTG, p < 0.01, r² = 0.88). This relationship was integrated into a population model to translate changes in VTG concentrations of female fathead minnows to alterations in population growth. The model predicted relatively profound effects on population size offish experiencing moderate decreases in vitellogenesis. For example, a fathead minnow population at a carrying capacity exposed to a chemical stressor that causes a 25% decrease in VTG concentration in females from baseline values would exhibit a 34.6% projected decrease in size after two years of exposure and reach an equilibrium population size that was only 30.2% of the preexposed population. Overall, the current study provides an example of how changes in a biomarker (VTG concentration) can be quantitatively translated into adverse effects at the individual and population levels.

Research on spermatozoal RNA has made considerable progress since the original reports on its presence appeared in the late 1950s and early 1960s. Through the use of stringent procedures aimed at eliminating contamination artefacts, we now appreciate that a complex cohort of mRNAs persists in the ejaculate cell but that 80S (cytoplasmic) ribosomal complexes are not present in sufficient quantities to support cytoplasmic mRNA translation. Despite this, under certain conditions, at least some cytoplasmic mRNAs can apparently be translated de novo, possibly on mitochondrial polysomes. The detection of mRNA translation by mature spermatozoa essentially supports the earliest research reports on spermatozoal gene expression although the suggested relationship with protein turnover and capacitation is wholly unexpected. We also examine some alternative explanations and roles for RNA carriage, including the RNAs passive retention as a consequence of nuclear shutdown and a more active role in chromatin repackaging, genomic imprinting, gene silencing and post-fertilization requirements of essential paternal RNAs. The recent report of an RNA-mediated epigenetic alteration to phenotype that is likely to be sperm derived is of particular interest in this regard. We finally show that regardless of the biological role(s) of spermatozoal RNA, its utility in infertility studies, particularly when coupled with modern techniques in gene-expression analysis (e.g. microarrays), is obvious. As a wholly non-invasive proxy for the testis, this RNA offers considerable potential as a marker for fertility status and the genetic and environmental influences that could make all the difference between a fertile and an infertile phenotype.