Polycystins and Male Fertility

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DESCRIPTION (provided by applicant): Successful fertilization requires the arrival of the spermatozoa at the oocyte in a fertile state; the process of capacitation thus represents one of the key aspects of male fertility. Although in vitro studies have identified a key series of biochemical state changes in spermatozoa which correlate with the acquisition of the capacitated state, the mechanisms which operate within the female reproductive tract, and their timing, are less clear. So while the female reproductive tract plays important roles in control of sperm capacitation, the biochemical basis of these regulatory events remain to be characterized. Mice which lack the germ line restricted polycystin pkdrej show alterations in sperm behavior, both in vitro and in vivo which are consistent with changes in the regulation of the capacitation process. The identification of aspects of the phenotype which appear to alter the behavior of sperm from mutant mice within the female tract suggests that these animals will be a useful tool to elucidate the mechanisms by which sperm transport within the oviduct is regulated. The current proposal aims to build on our preliminary observations and address in more detail the role the polycystin pkdrej plays in the regulation of male fertility. This proposal has two aims. 1) Examine why reduced numbers of these sperm reach the oocyte when compared to sperm from wildtype males. This aim will involve examining the movement of sperm within the female reproductive tract. 2) The use of in vitro capacitation assays to determine a possible biochemical basis for the altered behavior of sperm from males lacking pkdrej. Providing individuals with control of their fertility either in the context of contraception or in the treatment of infertility is a fundamental health issue. The factors affecting the movement of gametes within the female reproductive tract represent a key determinant of fertility. Understanding the factors that control these processes and the signaling pathways they target may provide new targets both for the control of fertilization and as a treatment strategy for infertility.