The sperm epigenome: A role in embryogenesis and fetal health?

It is interesting and instructive to note that the underlying foundations in our studies of fertilization and early embryogenesis are evolving. Until recently, the mechanisms and foci of research regarding events in the fertilization continuum have been largely based on sperm physiology (i.e. sperm motility, hyperactivation, capacitation, the acrosome reaction, zona binding, sperm chromatin decondensation, etc.), whereas post-fertilization embryogenesis events have been investigated almost exclusively from the perspective of the oocyte’s contribution to embryo competence and the transition of control in early embryogenesis to the embryo itself. However, it has become apparent that the sperm cell provides more than a “neutral” set of chromosomes to the oocyte [1]. Furthermore, it has been shown that in a subset of infertile couples undergoing in vitro fertilization (IVF), the sperm may be responsible for altered embryogenesis [2–4]. Several mechanisms exist by which sperm may affect embryogenesis, including DNA damage in the form of single- and double-strand breaks, chromosome aneuploidy, altered sperm-derived centrosome function, and sperm DNA packaging abnormalities through both “classical epigenetic” and “non-classical epigenetic” mechanisms. “Epigenetics” is defined as “the study of mitotically and/or meiotically heritable changes in gene function that can not be explained by changes in DNA sequence” [5]. A key component of this “classical” definition of epigenetics is the issue of heritability. While many sperm factors may ultimately affect gene transcription (i.e. DNA strand breaks or protamine packaging defects), such factors are usually not heritable. The two “classical” forms of epigenetic marks are DNA methylation and various chemical modifications on histone tails. Either of these epigenetic marks is sufficient to regulate gene activation independently, or in concert with each other.