Phosphatidylinositol 3-kinase inhibition enhances human sperm motility.
BACKGROUND
The number of spermatozoa with forward motility after capacitation procedures represents the limiting factor for application of IVF versus intracytoplasmatic sperm injection (ICSI) procedure in cases of oligoasthenozoospermia. 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 investigated the role of phosphatidylinositol 3-kinase (PI3K), a lipid and protein kinase involved in the regulation of several biological aspects of somatic cells, on human sperm motility by using the specific PI3K inhibitor LY294002.


RESULTS
We demonstrated that in-vitro incubation of swim-up selected or unselected human spermatozoa with LY294002 determined an increase of percentage forward motility in all the treated samples. The effect was dose-dependent with an EC(50) of 1.09 +/- 0.54 micromol/l. LY294002 also increased sperm movement characteristics and hyperactivation as evaluated by 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.
Luconi
M
M
Dipartimenti di Fisiopatologia Clinica, Unità di Andrologia, Università di Firenze, Italy.
Marra
F
F
Gandini
L
L
Filimberti
E
E
Lenzi
A
A
Forti
G
G
Baldi
E
E
D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013081:Sperm Motility / Q000187:drug effects / Q000502:physiology*; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology
D002867:Chromones; D009025:Morpholines; D016877:Oxidants; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006861:Hydrogen Peroxide; D018021:Lithium Chloride