The molecular basis of sperm - oocyte interactions

Abstract

Research Doctorate - Doctor of Philosophy (PhD)The remarkable cellular communication events that characterise the highly species specific interactions observed during the ontogeny of mammalian fertilization, represent some of the most intriguing in all of biology. Given the 60 years or so of research conducted to elucidate the precise mechanisms that underpin these interactions, it is surprising that they still remain largely unknown. This can be mostly attributed to the unique luminal environment in which the sperm reside following insemination and the direct effects that these fluids have on their functionality. Although immense controversy surrounds the precise ligand responsible for the spermatozoas binding to the oocyte’s zona pellucida, considerable contention is also afforded to the mechanism by which they bind. A number of landmark papers have recently emerged to suggest that these initial binding events may be facilitated by the formation and presentation of multimeric zona pellucida receptor complexes on the sperm surface during their terminal maturation, rather than the widely held paradigm that the zona pellucida receptor is a single molecular entity. During these studies the use of blue native polyacrylamide gel electrophoresis, for the first time in mammalian sperm, has provided direct evidence that a number of multimeric zona receptor complexes indeed reside on the apical plasma membrane of capacitated sperm and that two of these complexes have the ability to interact with the zona pellucida. Proteomic analysis of these two complexes has indicated that molecular chaperones (CCT/TRiC complex and HSPD1) are responsible for the formation of each complex, and individually, these complexes contain a number of receptor proteins (ZPBP2, ZP3R and ADAMTS10) that potentially provide the zona pellucida affinity. Collectively, these data provide an important biochemical insight into the molecular basis of sperm-zona pellucida interaction and a plausible explanation for how spermatozoa gain their ability to fertilize