Cellular mechanisms regulating sperm-zona pellucida interaction

Abstract

For mammalian spermatozoa to exhibit the ability to bind the zona pellucida (ZP) they must undergo three distinct phases of maturation, namely, spermatogenesis (testis), epididymal maturation (epididymis) and capacitation (female reproductive tract). An impressive array of spermatozoa surface remodeling events accompany these phases of maturation and appear critical for recognition and adhesion of the outer vestments of the oocyte, a structure known as the ZP. It is becoming increasingly apparent that species-specific zona adhesion is not mediated by a single receptor. Instead, compelling evidence now points toward models implicating a multiplicity of receptor-ligand interactions. This notion is in keeping with emerging research that has shown that there is a dynamic aggregation of proteins believed to be important in sperm-ZP recognition to the regions of sperm that mediate this binding event. Such remodeling may in turn facilitate the assembly of a multimeric zona recognition complex (MZRC). Though formation of MZRCs raises questions regarding the nature of the block to polyspermy, formation and assembly of such a structure would no doubt explain the strenuous maturation process that sperm endure on their sojourn to functional maturity.

Figure 1

Schematic representing the distinct changes in sperm surface architecture throughout the three stages of sperm maturation. Spermatogenesis, occurring in the testis, comprises the sequence of cell divisions and immense morphological alterations that convert the round spermatogonia (a) into large numbers of morphologically mature spermatozoa (b). Incorporated in this maturation process is the intrinsic expression of a number of proteins believed to participate in sperm–ZP interaction. Following spermatogenesis, spermatozoa then undergo a second phase of maturation, namely, ‘epididymal maturation' in which spermatozoa are bathed in a complex intraluminal milieu that appears to imbue the cells with a large number of proteins/molecules that are also necessary for successful fertilization (c). An additional modification is the uptake of DFs (X) that prevent the cells from undergoing premature capacitation. The final phase of sperm maturation, capacitation, occurs within the female reproductive tract and culminates in the acquisition of full functional competence. Two distinct events occur during the initial stages of capacitation, namely, cholesterol efflux, and removal of DFs (d). Following the loss of these inhibitory molecules, complex signaling pathways are activated that result in both the attainment of hyperactivated motility and ability to bind the ZP. Distinct membrane remodeling events accompany this process including phospholipid scrambling and a dynamic coalescence of lipid rafts and putative receptor molecules to sites on the apical margin of the sperm surface that are capable of ZP interaction (e). This process may also be augmented by the translocation of proteins, such as ZP3R, from within the acrosomal matrix to the sperm plasma membrane. Such events are likely facilitated via budding of the outer acrosomal membrane resulting in formation of fusion pores. Upon aggregation of receptor molecules, the assembly of MZRCs is predicted to occur through the concerted action of a subset of molecular chaperones, thus producing cells that exhibit the functional competence required for adhesion to the ZP. DF, decapacitation factor; MZRC, multimeric zona recognition complex; ZP, zona pellucida; ZP3R, ZP3 receptor.