CONICET | Buscador de Institutos y Recursos Humanos

Hormonal contraceptive methods are known to produce multiple side effects. Thus, there is a need to develop new and safer non-hormonal options. Contraceptive methods specifically targeting sperm function constitute an attractive approach for both male and female contraception. CatSper, the principal mammalian sperm calcium channel, is involved in the development of hyperactivation, a vigorous motility essential for fertilization and male fertility. Considering that CatSper is only expressed in sperm, it represents an excellent target for non-hormonal contraception. Based on this, in the present work, we evaluated the effect of HC, a specific Catsper inhibitor, on different sperm functional parameters. Our results show that exposure of cauda epididymal mouse sperm to different concentrations of HC (1, 5, 10 and 20 uM) during capacitation did not affect sperm viability but produced a significant decrease in their motility at concentrations  5 uM. A time course study using HC 10 uM showed that this effect becomes evident after 30 minutes of incubation, reaching levels lower than 5% at the end of capacitation (90 min). Whereas protein tyrosine phosphorylation, a capacitation-associated event, markedly decreased by exposure to > 5 uM, neither the spontaneous nor the ionophore-induced acrosome reaction were affected at any of the HC concentrations employed. Experiments in which cumulus oocytes complexes or zona-free eggs were co-incubated with sperm capacitated in the presence of HC (1 to 20 uM) showed a significant decrease in the percentage of penetrated eggs at 5 uM with a complete inhibition at  10 uM. The fact that the presence of HC only during gamete co-incubation neither affected fertilization nor egg penetrability confirmed that HC mainly affects sperm capacitation. Together, these results indicate that HC is specifically interfering with the sperm fertilizing ability, supporting its potential use for non-hormonal contraceptive development.