Aberrant protamine content in sperm and consequential implications for infertility treatment

Human sperm express two types of protamine: protamine 1 (P1) and the family of protamine 2 (P2) proteins, with P1 and P2 normally existing in a ratio of approximately 1:1. Both the elevation and reduction of this ratio have been linked with male infertility suggesting that abnormalities in protamine expression, processing and replacement may be responsible for effects on semen parameters observed in infertile males affected by deficient protamination, along with abnormalities in associated regulatory processes. Abnormal protamination may result in insufficient condensation in the sperm nucleus, thus rendering paternal DNA susceptible to damage, which could have detrimental consequences upon embryogenesis. Consequently, it is imperative that Assisted Reproductive Technologies (ARTs) endeavour to utilise sperm devoid of protamine abnormalities, especially because retained histones are present in imprinted gene clusters. Emerging evidence indicates that abnormalities in protamine content may influence epigenetic signals transmitted via paternal DNA. Indeed, an increase in rare imprinting disorders has been observed in children conceived via in vitro fertilisation (IVF). This review examines the links between male infertility, abnormal protamine expression and replacement, the implications of abnormal sperm DNA packaging on fertility treatments and the potential iatrogenic effects of ART procedures on sperm function.