Oviductal regulation of gamete interaction and reproductive function

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The mammalian oviduct undergoes physiological and biochemical modifications during late follicular development and estrus. These hormonally regulated changes optimize the oviductal microenvironment for fertilization and early embryonic development. A major glycoprotein secreted by oviductal cells, known as oviductin, is conserved across a number of mammalian species. In the hamster model used in our laboratory, oviductin is an O-glycosylated protein that undergoes cyclic variation of glycosylation during the estrous cycle. We have published extensively on the biosynthesis, secretion, localization and biochemical properties of hamster oviductin (HamOVGP1). During the tenure of my last NSERC DG, we demonstrated, for the first time, the ability of HamOVGP1 to enhance capacitation by potentiating tyrosine phosphorylation of a subset of sperm proteins known to play specific roles in sperm function. Our results further support an important role for oviductin in the oviductal milieu during the early events of fertilization. Recently, we have successfully produced recombinant hamster oviductin (rHamOVGP1) in HEK293 cells. Our recent work supported by NSERC reaffirms our laboratory in the forefront and as an authority in the field of mammalian oviductin. Based on our previous studies showing localization of oviductin to the cell surface of a subpopulation of epithelial cells of the hamster endometrium, we hypothesize that a putative oviductin receptor is present at the cell surface of certain uterine cells and that this receptor may play an important role in uterine receptivity. We plan 1) to examine the role of glycocomponents of rHamOVGP1 in enhancing sperm capacitation through enhancement of tyrosine phosphorylation of sperm proteins, and to assess the effect of glycan and glycopeptide derivatives of rHamOVGP1 in sperm-egg binding and fertilization; 2) to determine the mechanism of how rHamOVGP1 mediates signal transduction pathways that regulate protein tyrosine phosphorylation, and 3) to identify and characterize hamster oviductin receptor and to produce recombinant receptor for testing its possible role in uterine receptivity. To date, the mechanism of oviductin regulating the enhancement of capacitation and sperm-egg binding remains an enigma. Using the rHamOVGP1 that we successfully produced during the tenure of my last NSERC DG, it is now possible to unravel the mechanism of oviductin that regulates some of the key events that lead to successful fertilization and the possible role of oviductin in early implantation. It is anticipated that results obtained from this study will lead to the development of a suitable "drug cocktail" therapy utilizing oviductin and its glycan derivatives for improving the insemination procedures involving farm animals in the Canadian agriculture industry as well as IVF procedures involving rodents in research laboratories.***