The Clinical Utility of the Protamine 1/Protamine 2 Ratio in Sperm

Laszlo      Nanassy; Lihua      Liu; Jeanine      Griffin; Douglas      T. Carrell

Abstract

During spermiogenesis, human sperm undergo a dramatic reorganization of the chromatin in which canonical histones are replaced by two types of protamines, protamine 1 (P1) and protamine (P2). P1 and P2 are expressed approximately at a 1:1 ratio in healthy men. Alteration of this ratio is associated with male infertility. Patients with an abnormal P1/P2 ratio generally exhibit diminished semen quality, lower fertilization ability, and lower pregnancy rates when undergoing in vitro fertilization. Many studies have reported an elevated incidence of abnormal P1/P2 ratios in infertile men compared to fertile controls, and have evaluated the relationship between infertility and abnormal protamination; however, no prospective study has investigated the normal range of the P1/P2 ratio in men from the general population. Here, we report a P1/P2 reference range of 0.54 to 1.43 in a fertile, normozoospermic population. This rather wide normal range of P1/P2 led us to the conclusion that abnormal protamination is more likely indicative of other perturbations during spermatogenesis than the underlying mechanism to cause infertility. Alternatively, protamine expression may act as a checkpoint mechanism and thus be indirectly related to semen quality.

Keywords: Sperm chromatin, male infertility, protamine, embryogenesis, epigenetics, canonical histones, protamination, Loci, Angleman syndromes, spermiogenesis, chromatin remodeling, embryonic transcription, Semen, perturbation, somatic histones, gametes, normozoospermic, aneuploidy, Fertilization, cleavage rateSperm chromatin, male infertility, protamine, embryogenesis, epigenetics, canonical histones, protamination, Loci, Angleman syndromes, spermiogenesis, chromatin remodeling, embryonic transcription, Semen, perturbation, somatic histones, gametes, normozoospermic, aneuploidy, Fertilization, cleavage rate