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

TLDR

A high sperm protamine‑1 to protamine‑2 ratio has been linked to male infertility. The study examined whether a decreased P1/P2 ratio is also associated with infertility and sought to explain the underlying protein‑expression abnormalities by quantifying P1 and P2 in 272 infertile men and 87 fertile donors. Protamine ratios and total protamine amounts were correlated with fertility status using semen analysis, sperm penetration capacity, and IVF outcomes, revealing four distinct groups: normal‑ratio fertile donors, normal‑ratio patients, low‑ratio patients, and high‑ratio patients. Patients with abnormal P1/P2 ratios—low or high—displayed altered protamine expression, diminished semen quality and sperm penetration, and the study identified a novel infertile subgroup with a reduced ratio caused by abnormal P1 or P2 concentrations.

Abstract

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.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.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.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.