Introduction: the malleable sperm genome

Over the last decade, our assumptions and ideas about the stability of the mammalian sperm genome have gone through a gentle and progressive change. Historically, we viewed the sperm genome as tightly packaged into a virtual crystalline state with very little biochemical accessibility. We now understand that in many cases of decreased male fertility sperm deoxyribonucleic acid (DNA) structure loses much of this inaccessibility and that the DNA is susceptible to damage. More recently, evidence has emerged from many different laboratories that spermatozoa contain nucleases that are capable of digesting their compact DNA. These data suggest that the sperm genome may be less stable than we thought and might even be flexible enough to regulate its own stability in a manner similar to somatic cells. In this review, we will explore the current status of the stability of the mammalian sperm genome in the context of what is known about sperm chromatin structure.

Sperm chromatin structure and fertility

Before discussing DNA damage as it relates to sperm chromatin structure we will briefly review those aspects of sperm chromatin, both known and suspected, that pertain to this discussion. During spermiogenesis the haploid sperm chromatin undergoes one of the most significant changes known in biology. All of the histones are replaced first by transition proteins, then by protamines (Meistrich et al., 2003).