Investigation of the mechanisms by which the molecular chaperone HSPA2 regulates the expression of sperm surface receptors involved in human sperm-oocyte recognition

Abstract

A unique characteristic of mammalian spermatozoa is that, upon ejaculation, they are unable to recognize and bind to an ovulated oocyte. These functional attributes are only realized following the cells' ascent of the female reproductive tract whereupon they undergo a myriad of biochemical and biophysical changes collectively referred to as 'capacitation'. We have previously shown that this functional transformation is, in part, engineered by the modification of the sperm surface architecture leading to the assembly and/or presentation of multimeric sperm -oocyte receptor complexes. In this study, we have extended our findings through the characterization of one such complex containing arylsulfatase A (ARSA), sperm adhesion molecule 1 (SPAM1) and the molecular chaperone, heat shock 70kDa protein 2 (HSPA2). Through the application of flow cytometry we revealed that this complex undergoes a capacitation-associated translocation to facilitate the repositioning of ARSA to the apical region of the human sperm head, a location compatible with a role in the mediation of sperm -zona pellucida (ZP) interactions. Conversely, SPAM1 appears to reorient away from the sperm surface, possibly reflecting its primary role in cumulus matrix dispersal preceding sperm -ZP recognition. The dramatic relocation of the complex was completely abolished by incubation of capacitating spermatozoa in exogenous cholesterol or broad spectrum protein kinase A (PKA) and tyrosine kinase inhibitors suggesting that it may be driven by alterations in membrane fluidity characteristics and concurrently by the activation of a capacitation-associated signal transduction pathway. Collectively these data afford novel insights into the sub-cellular localization and potential functions of multimeric protein complexes in human spermatozoa.

Factors and pathways involved in capacitation: how are they regulated?

“…In a recent report from Bromfield, they postulate that the clinical disruption of sperm-zona pellucida binding may be facilitated by defects in the heat shock protein A2-mediated assembly of zona-recpetor complexes on the sperm surface during capacitation. They found oxidative stress during human sperm capacitation trigger the chemical alkylation of the molecular chaperone heat shock protein A2, a concomitant reduction in surface expression of the zona pellucida-receptor arylsulphatase A and a severe loss of zona pellucida binding ability, which may strongly related to the zona-pellucida binding [154, 270]. …”

Oviductal secretion and gamete interaction

“…It has also been involved in the binding of acrosome-reacted sperm to the ZP (Myles & Primakoff 1997, Redgrove et al 2013.…”

Sperm DNA Fragmentation Index and Hyaluronan Binding Ability in Men from Infertile Couples and Men with Testicular Germ Cell Tumor

“…One test which is gaining popularity is the Hyaluronan Binding Assay (HBA), based on the observation that sperm binding to hyaluronic acid (HA) plays a critical role in the selection of mature, functionally competent spermatozoa during in vivo [19] and in vitro fertilization [20]. HA is a linear polysaccharide present in the extracellular matrix of cumulus oophorus around the oocyte.…”