Protamines and male infertility

Abstract

Protamines are the major nuclear sperm proteins. The human sperm nucleus contains two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single gene that is transcribed and translated into a precursor protein. The protamines were discovered more than a century ago, but their function is not yet fully understood. In fact, different hypotheses have been proposed: condensation of the sperm nucleus into a compact hydrodynamic shape, protection of the genetic message delivered by the spermatozoa, involvement in the processes maintaining the integrity and repair of DNA during or after the nucleohistone-nucleoprotamine transition and involvement in the epigenetic imprinting of the spermatozoa. Protamines are also one of the most variable proteins found in nature, with data supporting a positive Darwinian selection. Changes in the expression of P1 and P2 protamines have been found to be associated with infertility in man. Mutations in the protamine genes have also been found in some infertile patients. Transgenic mice defective in the expression of protamines also present several structural defects in the sperm nucleus and have variable degrees of infertility. There is also evidence that altered levels of protamines may result in an increased susceptibility to injury in the spermatozoan DNA causing infertility or poor outcomes in assisted reproduction. The present work reviews the articles published to date on the relationship between protamines and infertility.

The predictive value of high-magnification sperm morphology examination on ICSI outcomes in the presence of oocyte dysmorphisms

“…It has been shown that sperm with protamine deficiency and increased histone remnants, lead to premature chromatin condensation that is the cause of failures in fertilization and embryo development [16,33].…”

A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART)

“…The lack of proper DNA packaging in sperm has been associated with infertility in mice [160]. During the chromatin re-packaging in spermatogenesis process, about 85 % of the histones are replaced by protamines [161]. In the initial stages of spermiogenesis, histones are hyper acetylated and undergo other modifications [162].…”

Single nucleotide polymorphisms in the SEPTIN12 gene may be associated with azoospermia by meiotic arrest in Japanese men

“…Genetic causes of azoospermia in humans include chromosomal abnormalities, e.g., Y-chromosome microdeletions and mutations in specific genes; e.g., DAZ, SYCP3, PRM1, SPATA16, AURKC and KLHL10 [1][2][3][4][5][6][7]. As Y-chromosome deletions account for only 16% of men with infertility [8], azoospermia in many infertile men may be caused by mutations in autosomal genes.…”