Impact of sperm protamine on semen quality and fertility

Abstract

Protamines are the nuclear proteins essential for chromatin compaction during spermatogenesis. During chromatin compaction, histones are replaced by transition proteins, which are then replaced by protamines. This process is essential for DNA stability. Protamines are rapidly evolved proteins with high evolutionary variation and encompass positively charged amino acids, especially 48% of arginine. Cysteines present in their sequence allow the formation of disulfide bonds between adjacent protamine molecules. Protamine 1 (PRM1), Protamine 2 (PRM2), and Protamine 3 (PRM3) are reported in mammals. Among these, PRM1 and PRM2 were extensively studied. The normal PRM1 and PRM2 ratios in men, stallions, and mice are 1:1, 3:1, and 1:2, respectively. However, in infertile males, the PRM1: PRM2 ratio is altered due to decreased PRM2 expression, which, in turn, is due to incomplete PRM2 precursor processing and zinc deficiency. In bull, ram, and buck, PRM2 mRNA is present but not PRM2 protein. In mice, rats, bulls, and men, the protamine cluster contains an open reading frame called protamine 3 (gene-4 or protamine-3). The proportion of protamine deficient sperm in the sample is indicative of problems in protamination. Recently, omics technologies, RT-qPCR, and gene knockout-based studies also reported the presence of protamine in sperm. All these semen quality and knockout studies envisage that protamines are indispensable for fertility. Henceforth, protamine-like biomolecules also may be evaluated for fertility prediction or markers in addition to the existing structural and functional attributes of sperm.

Epigenetics in Reproductive Aging: Involvement of Oxidative Stress

“…Therefore, patients having a P1/P2 ratio less than 0.8 demonstrate insufficient DNA condensation and the characteristics of sperm (such as motility, viability, vitality, and counts, and morphology) are resultantly altered. A lower P1/P2 ratios may also be linked with an increased DNA fragmentation, which in contrary manner have correlations with the levels of global sperm P1 and P2 [71,72]. This confers a protective role on protamines against sperm DNA damage.…”