CONICET | Buscador de Institutos y Recursos Humanos

Hormonal contraceptivemethods are known to produce multiple side effects. Thus, there is a need todevelop new and safer non-hormonal options. Contraceptive methods specificallytargeting sperm function constitute an attractive approach for both male andfemale contraception. CatSper, the principal mammalian sperm calcium channel,is involved in the development of hyperactivation, a vigorous motilityessential 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 theeffect of HC, a specific Catsper inhibitor, on different sperm functionalparameters. Our results show that exposure of cauda epididymal mouse sperm to differentconcentrations of HC (1, 5, 10 and 20 uM) during capacitation did not affectsperm viability but produced a significant decrease in their motility atconcentrations ³ 5 uM. A time course study using HC 10 uM showed that this effectbecomes evident after 30 minutes of incubation, reaching levels lower than 5% atthe end of capacitation (90 min). Whereas protein tyrosine phosphorylation, acapacitation-associated event, markedly decreased by exposure to > 5 uM, neitherthe spontaneous nor the ionophore-induced acrosome reaction were affected atany of the HC concentrations employed. Experiments in which cumulus oocytes complexes orzona-free eggs were co-incubated with sperm capacitated in the presence of HC (1to 20 uM) showed a significant decrease in the percentage of penetrated eggs at5 uM with a complete inhibition at ³ 10 uM. Thefact that the presence of HC only during gamete co-incubation neither affectedfertilization nor egg penetrability confirmed that HC mainly affects spermcapacitation. Together, these results indicate that HC is specificallyinterfering with the sperm fertilizing ability, supporting its potential usefor non-hormonal contraceptive development.