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


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.
Luconi
Michaela
M
Department of Clinical Physiopathology, Center of Research, Transfer and High Education, DENOthe Andrology Unit, University of Florence, Italy.
Torcia
Simona
S
Grillo
Domenico
D
Fiorenza
Maria Teresa
MT
Forti
Gianni
G
Mangia
Franco
F
Baldi
Elisabetta
E
D000818:Animals; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects*; D015153:Blotting, Western; D002867:Chromones / Q000494:pharmacology*; D015925:Cryopreservation; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D047108:Embryonic Development; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004822:Epididymis / Q000473:pathology; D005260:Female; D005306:Fertilization; D006801:Humans; D007053:Ice; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D013075:Sperm Capacitation; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D002867:Chromones; D004791:Enzyme Inhibitors; D007053:Ice; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one