Phosphatidylinositol 3-kinase inhibition enhances human sperm motility

BACKGROUND: The number of spermatozoa with forward motility after capacitat ion procedures represents the limiting factor for application of IVF versus intracytoplasmatic sperm injection (ICSI) procedure in cases of oligoasthe nozoospermia. The possibility of increasing this number may thus be of help to the patient. A complex array of signalling pathways is involved in the regulation of sperm motility and recent data pointed out an important role for kinase/phosphatase-regulated phosphorylation of proteins. Here, we inve stigated the role of phosphatidylinositol 3-kinase (PI3K), a lipid and prot ein kinase involved in the regulation of several biological aspects of soma tic cells, on human sperm motility by using the specific PI3K inhibitor LY2 94002. METHODS AND RESULTS: We demonstrated that in-vitro incubation of swi m-up selected or unselected human spermatozoa with LY294002 determined an i ncrease of percentage forward motility in all the treated samples. The effe ct was dose-dependent with an EC50 of 1.09 +/-0.54 mu mol/l. LY294002 also increased sperm movement characteristics and hyperactivation as evaluated b y computer-assisted motion analyser. The compound was also able to overcome the detrimental effect of hydrogen peroxide and lithium chloride on sperm motility. CONCLUSIONS: Our results suggest a negative role for PI3K in the development and maintenance of sperm motility and suggest a possible use of PI3K inhibitors to enhance motility in cases of asthenozoospermia.