Enhancement of mouse sperm motility by the PI3-kinase inhibitor LY294002 does not result in toxic effects on preimplantation embryo development

Abstract

Background: A reduced number of progressively motile sperm (as may occur in cases of asthenozoospermia or when cryopreserved spermatozoa are used for fertilization) limits the possibility of applying various assisted reproductive techniques (ARTs). We previously showed that incubation of sperm with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 increases sperm progressive motility and enhances the number of sperm recovered by capacitation protocols used in ART. Methods and Results: In the present study, we investigate the motility-enhancing effects of this compound in epididymal mouse sperm, and examine the use of the mouse system to investigate the effect of LY294002 on oocyte fertilization and preimplantation embryo development. Our results show that neither pre-incubation of mouse spermatozoa with the inhibitor during in vitro capacitation nor the direct addition of LY294002 to the sperm-oocyte mixture significantly affects the process of fertilization and preimplantation development of embryos produced even when they developed in the presence of LY294002. Conclusions: The present data encourage the design of new drugs based on the molecular structure of LY294002, which may open up new options for the in vitro treatment of human/animal asthenozoospermia. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.