Grant: Operating Grant

Infertility is now estimated to effect 70 million couples worldwide, about 40% of who suffer from male infertility. A key treatment technique for infertile couples is intracytoplasmic sperm injection (ICSI), whereby a sperm is microinjected directly into the oocyte. However, ICSI is only 40% successful. Treatment failure could be due to the sperm's inability to induce fertilization because of the absence of a sperm-borne oocyte activating factor (SOAF) that has not yet been identified. We have recently identified and partially characterized a strong SOAF candidate protein known as PAWP. In this project we advance our findings by understanding the mechanism of action of PAWP during fertilization in the mouse and confirming it in human fertilization. Infertile patients will also be screened for the expression level of PAWP as a potential diagnostic biomarker. Identification of this factor as a non-redundant SOAF and understanding the mechanism of its action will help translate our basic knowledge into developing a new diagnostic tool for male infertility. For assurance we will also eliminate the PAWP gene in the mouse and use this infertile knockout model to investigate new methods for the treatment of infertility. We can then validate recombinant PAWP as a biological supplement to increase the success rate of ICSI.