CATSPER is a family of sperm-specific calcium channels activated by P in human spermatozoa (Lishko et al. 2011, Strunker et al. 2011). KO mice for CATSPER are infertile due to severe defects in sperm motility.
We studied the involvement of CATSPER in human sperm motility and P responsiveness.
Western blot analysis with an anti-CATSPER1 antibody demonstrated the presence of three major bands corresponding to CATSPER1, 2 and 34. By immunoflorescence we observed that channels are mainly located in the principal piece of the tail. Higher levels of CATSPER were found by flow cytometry analysis in swim up selected spermatozoa respect to unselected (50.9±16.6 vs 23.4±10.7, n=6, P=0.01). To investigate the role of CATSPER channels in human sperm motility, we evaluated the effects of the specific inhibitor NNC55-0396 (10 and 20 μM) and the non specific inhibitor mibefradil (30 and 40 μM) on swim up selected spermatozoa (n=13) by CASA system. Both compounds significantly inhibited several motility-parameters (VAP, VCL, VSL, BCF and STR). We evaluated the effect of mibefradil and NNC55-0396 on P (10 μM)-stimulated AR in swim up selected human sperm (n=11). Mibefradil at 30 μM was ineffective, whereas a 50% inhibition was observed at 40 μM. Conversely, NNC55-0396 compound, tested at 10 μM concentration, inhibited P-induced AR of 70%.
These results indicate that CATSPER calcium channels are involved in human sperm motility and P-induced AR. In light of a recent study (Jin et al. 2011) demonstrating that physiological AR occurs during transit in the cumulus matrix of the oocyte (where P is present at μM concentrations) before sperm attachment to the zona pellucida, our data suggest that CATSPER may be considered a possible molecular target for the development of novel therapeutic strategies for male infertility as well as for male-directed contraception.
27 Apr - 01 May 2013
European Society of Endocrinology