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

Felipe A. Navarrete, Antonio Alvau, Hoi Chang Lee, Lonny R. Levin, Jochen Buck, Patricia Martin De Leon, Celia M. Santi, Dario Krapf, Jesse Mager, Rafael A. Fissore, Ana M. Salicioni, Alberto Darszon, Pablo E. Visconti

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Abstract

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.

Original languageEnglish
Article number33589
JournalScientific reports
Volume6
DOIs
StatePublished - Sep 15 2016

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    Navarrete, F. A., Alvau, A., Lee, H. C., Levin, L. R., Buck, J., Leon, P. M. D., Santi, C. M., Krapf, D., Mager, J., Fissore, R. A., Salicioni, A. M., Darszon, A., & Visconti, P. E. (2016). Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models. Scientific reports, 6, [33589]. https://doi.org/10.1038/srep33589