Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models

Mammalian sperm acquire fertilizing capacity in the female tract in a process called capacitation. At the molecular level, capacitation requires protein kinase A activation, changes in membrane potential and an increase in intracellular calcium. Inhibition of these pathways results in loss of fertilizing ability in vivo and in vitro. We demonstrated that transient incubation of mouse sperm with Ca 2+ ionophore accelerated capacitation and rescued fertilizing capacity in sperm with inactivated PKA function. We now show that a pulse of Ca2+ ionophore induces fertilizing capacity in sperm from infertile CatSper1 (Ca2+ channel), Adcy10 (soluble adenylyl cyclase) and Slo3 (K+ channel) KO mice. In contrast, sperm from infertile mice lacking the Ca 2+ efflux pump PMACA4 were not rescued. These results indicate that a transient increase in intracellular Ca 2+ can overcome genetic infertility in mice and suggest this approach may prove adaptable to rescue sperm function in certain cases of human male infertility.Fil: Navarrete, Felipe A.. University of Massachusetts; Estados UnidosFil: Alvau, Antonio. University of Massachusetts; Estados UnidosFil: Lee, Hoi Chang. University of Massachusetts; Estados UnidosFil: Levin, Lonny R.. Weill Cornell Medical College; Estados UnidosFil: Buck, Jochen. Weill Cornell Medical College; Estados UnidosFil: Leon, Patricia Martin De. University of Delaware; Estados UnidosFil: Santi, Celia M.. University of Washington; Estados UnidosFil: Krapf, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Mager, Jesse. University of Massachusetts; Estados UnidosFil: Fissore, Rafael A.. University of Massachusetts; Estados UnidosFil: Salicioni, Ana M.. University of Massachusetts; Estados UnidosFil: Darszon, Alberto. Universidad Nacional Autónoma de México. Instituto de Biotecnología; MéxicoFil: Visconti, Pablo E.. University of Massachusetts; Estados Unido