Foresta C, Pati MA, Perilli L, Menegazzo M, Zuccarello D, Ferlin A, Garolla A.

Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical 11 Pathology, Centre for Male Gamete Cryopreservation, University of Padua, Padua, Italy.

Background: Phosphodiesterase-5A (PDE5A) selective inhibitors are widely used in the management of erectile dysfunction. It has been reported the expression of mRNA for PDE5 in human spermatozoa but data on its role on sperm function are still controversial. Aim: Analysis of the expression of PDE5A in human spermatozoa and the evaluation of the in vitro effect of PDE5 inhibition on human sperm function. Material/Subjects and Methods: Semen samples of ten normozoospermic subjects were incubated with Tadalafil and Vardenafil at concentrations ranging from10-6M, to 10-12 M for up to 6 hours. We assessed the expression of PDE5A isoforms, the localization of the protein in the sperm cell, and evaluated the effect of the exposure to PDE5 inhibitors on sperm motility, intracellular cGMP and calcium levels, capacitation, acrosome reaction, apoptosis and fertilizing ability of human spermatozoa. Results: Isoforms A1 and A2 of the enzyme are expressed in the neck and acrosomal region of spermatozoa. The percentage of progressive motility, velocity parameters (VSL, VCL and VAP) and intracellular calcium concentration were significantly higher in sperm incubated with PDE5 inhibitors 10-6M compared to control sample at each time point. No differences were observed in both sperm capacitation and acrosome reaction, apoptosis and hamster egg penetration test. Conclusions: We showed for the first time the localization of PDE5A in human sperm and that its pharmacological inhibition positively influences sperm motility and intracellullar calcium concentration likely due to the enhancement of intracellular cGMP levels.