The Sperm Epigenome: Implications for the Embryo

Abstract

Recent advances, including the human genome project and numerous studies of cancer and other diseases, have shown that the genetic code is not simply limited to the sequence of the four bases of DNA but also includes epigenetic programming, heritable changes that affect gene expression [Riggs A, Martinssen R, Russo V (2007) Introduction. In: Riggs A, Martinssen R, Russo V (eds) Epigenetics mechanisms of gene regulation. Cold Spring Harbor Press, New York]. The science of epigenetics is important in understanding many diseases and biological processes, including in identifying the causes of disease and better understanding the mechanisms by which the environment can affect gene expression [Carrell Fertil Steril 97 (2):267-274, 2012]. This chapter will focus on the epigenome of sperm and particularly highlight the potential role of the sperm epigenome in embryogenesis.The sperm epigenome is unique and highly specialized because of the unique nature and function of sperm and because of the diverse requirements for successful fertilization. Due to the need for motility, sperm chromatin must be compacted and highly organized. During spermiogenesis the chromatin is packaged tightly into the sperm head by the replacement of most histones with protamines. This allows for protection of the DNA from the hostile environment in the female reproductive tract. Remaining histones can have chemical modifications to the tails of the protein that either facilitate or repress gene transcription. Sperm, like embryonic stem cells, have a unique pattern of histone modifications that includes both activating and silencing marks in the promoters of genes associated with development. These bivalent marks, along with DNA hypomethylation, comprise a unique state in which the key genes are "poised" for possible activation in embryogenesis. Sperm epigenetic abnormalities have been linked with multiple diseases including male factor infertility and poor embryogenesis.

Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development

“…sperm), as the male gamete, are responsible for not only delivering the paternal genome, but also for providing essential factors for fertilization and preimplantation embryonic development (Krawetz, 2005;Sone et al, 2005). Recent data also suggest that in addition to the paternal proteins and genome, sperm also contribute the paternal epigenome in the forms of specific paternal DNA methylation, retained histones and sperm-borne RNAs during fertilization and early embryonic development (Gannon et al, 2014;Jenkins and Carrell, 2012). Both coding and noncoding RNAs have been detected in sperm (Krawetz, 2005;Pessot et al, 1989) and small noncoding RNA (sncRNA) species including microRNAs (miRNAs) (Amanai et al, 2006;Yan et al, 2008), endogenous small interfering RNAs (endo-siRNAs) (Song et al, 2011), piwi-interacting RNAs ( piRNAs) (Ghildiyal and Zamore, 2009;Grivna et al, 2006), and tRNA-derived small RNAs (Kawano et al, 2012;Peng et al, 2012) appear to be abundant in sperm.…”

Transgenerational epigenetic programming via sperm microRNA recapitulates effects of paternal stress

“…Rodent models examining paternal transmission have identified epigenetic signatures in mature sperm as possible substrates of transgenerational programming, namely patterns of retained histone modifications, DNA methylation, and/or populations of small noncoding RNAs (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). RNA populations are of primary interest, as they may be altered through intercellular communication via epididymosomes even in transcriptionally inert mature sperm, where DNA condensation impedes other epigenetic change (22)(23)(24). Studies in which manipulation of total RNA content in postfertilization zygotes reproduced aspects of a paternally transmitted phenotype highlight the critical importance of RNA as a germ cell epigenetic mark and support the potential role of small RNAs, including microRNAs (miRs), in trait transmission (20,25).…”

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

“…Yamauchi et al (2011) (Yamauchi et al 2011) categorized at least six different kinds of epigenetic information in mammalian sperm: sperm chromatin-associated proteins, perinuclear theca proteins, DNA loop configuration by the sperm nuclear matrix, DNA methylation, histone modifications, and sperm RNAs. These recent findings reveal the complexity of paternal information delivered by the sperm, which requires a correct protamination, sufficient histone retention and a specific pattern of DNA methylation and histone modifications to achieve a successful fertilization (Gannon et al 2014).…”

“…The special nucleosome retention is not a random process, rather is a programmatic event to retain histones at key loci for embryo development with a contribution to totipotency, developmental decisions and imprinting patterns (Brykczynska et al 2010;Hammoud et al 2009;Arpanahi et al 2009). The special nuclear configuration of the mature gamete is reached thanks to ordered epigenetic changes taking place during the spermatogenetic process and is considered crucial for a suitable sperm function (Gannon et al 2014;O'Doherty and McGettigan 2014;Schagdarsurengin et al 2012). Anomalous retention of histones has been noticed at promoters of developmental-related genes in many infertile men (Hammoud et al 2011), reflecting the major function that this impaired situation could have in infertility.…”