The Molecular Chaperone HSPA2 Plays a Key Role in Regulating the Expression of Sperm Surface Receptors That Mediate Sperm-Egg Recognition

Abstract

A common defect encountered in the spermatozoa of male infertility patients is an idiopathic failure of sperm–egg recognition. In order to resolve the molecular basis of this condition we have compared the proteomic profiles of spermatozoa exhibiting an impaired capacity for sperm-egg recognition with normal cells using label free mass spectrometry (MS)-based quantification. This analysis indicated that impaired sperm–zona binding was associated with reduced expression of the molecular chaperone, heat shock 70 kDa protein 2 (HSPA2), from the sperm proteome. Western blot analysis confirmed this observation in independent patients and demonstrated that the defect did not extend to other members of the HSP70 family. HSPA2 was present in the acrosomal domain of human spermatozoa as a major component of 5 large molecular mass complexes, the most dominant of which was found to contain HSPA2 in close association with just two other proteins, sperm adhesion molecule 1 (SPAM1) and arylsulfatase A (ARSA), both of which that have previously been implicated in sperm-egg interaction. The interaction between SPAM1, ARSA and HSPA2 in a multimeric complex mediating sperm-egg interaction, coupled with the complete failure of this process when HSPA2 is depleted in infertile patients, provides new insights into the mechanisms by which sperm function is impaired in cases of male infertility.

The humanRHOXgene cluster: target genes and functional analysis of gene variants in infertile men

“…Several of these RHOX-regulated genes have been shown to have crucial roles in human male reproduction. For example, idiopathic infertile men who completely lack HSPA2 in their sperm exhibit impaired fertilizing ability (31,34) and reduced expression of HSPA1A in ejaculated sperm has been implicated in the pathogenesis of male infertility (35).…”

Oviduct: roles in fertilization and early embryo development

“…Heat shock protein member A2 (HSPA2) is present in the human spermatozoa and binds with arylsulfatase A (ARSA) and sperm adhesion molecule 1 (SPAM1) (Redgrove et al 2012, 2013, Bromfield et al 2016. Both ARSA and SPAM1 are detected in the rabbit and mouse oviduct (Vitaioli et al 1996, Griffiths et al 2008.…”

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

“…Other HSPs were observed in this study, of which we highlight the conserved Heat Shock-Related 70 kDa Protein 2 (HSPA2). HSPA2 was suggested as an important protein for sperm-egg recognition and fusion during fertilization [54]. Lima et al [55] demonstrated that adolescents with varicocele and unaltered semen when compared to age-matched controls presented an overexpression in the HSPA2 gene, not observed in adolescents with varicocele and altered semen.…”