Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males

BACKGROUND: A significant relationship exists between an abnormally high sperm protamine-1 (P1)/protamine-2 (P2) ratio and male infertility. In this study we investigate whether a decreased P1/P2 ratio is also linked to male infertility and we attempt to describe, at the protein expression level, the underlying cause of sperm P1/P2 deregulation. METHODS: P1 and P2 protein concentrations were quantified in sperm from 272 infertility patients and 87 fertile donors. P1/P2 ratios and protamine quantity were correlated with fertility status using semen analysis, sperm penetration capacity, and IVF data. RESULTS: We identified four distinct groups in the study: normal P1/P2 fertile donors, normal P1/P2 patients, low P1/P2 patients, and high P1/P2 patients. P1 and P2 were both under-expressed in patients with a normal P1/P2 ratio, but not in fertile donors. In patients with a low P1/P2 ratio, P1 was under-expressed while P2 was over-expressed; in patients with a high P1/P2 ratio, P1 was normally expressed and P2 was under-expressed. Patients with abnormal P1/P2 ratios displayed significantly reduced semen quality and sperm penetration ability. CONCLUSIONS: We have identified a novel population of infertile males with a reduced P1/P2 ratio. Aberrant P1/P2 ratios arise from an abnormal concentration of P1 and/or P2, either of which is associated with male infertility.