Sperm chromatin: fertile grounds for proteomic discovery of clinical tools

Sperm are remarkably complex cells with a singularly important mission: to deliver paternal DNA and its associated factors to the oocyte to start a new life. The integrity of sperm DNA is a keystone of reproductive success, which includes fertilization and embryonic development. In addition, the significance in these processes of proteins that associate with sperm DNA is increasingly being appreciated. In this review, we highlight proteomic studies that have identified sperm chromatin proteins with fertility roles that have been validated by molecular studies in model organisms or correlations in the clinic. Up to 50% of male-factor infertility cases in the clinic have no known cause and therefore no direct treatment. In-depth study of the molecular basis of infertility has great potential to inform the development of sensitive diagnostic tools and effective therapies that will address this incongruity. Because sperm rely on testis-specific protein isoforms and post-translational modifications for their development and function, sperm-specific processes are ideal for proteomic explorations that can bridge the research lab and fertility clinic.