Title | Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Navarrete FA, Alvau A, Lee HChang, Levin LR, Buck J, De Leon PMartin-, Santi CM, Krapf D, Mager J, Fissore RA, Salicioni AM, Darszon A, Visconti PE |
Journal | Sci Rep |
Volume | 6 |
Pagination | 33589 |
Date Published | 2016 09 15 |
ISSN | 2045-2322 |
Keywords | Adenylyl Cyclases, Animals, Calcimycin, Calcium Channels, Calcium Ionophores, Disease Models, Animal, Fertilization, Fertilization in Vitro, Infertility, Male, Large-Conductance Calcium-Activated Potassium Channels, Male, Mice, Inbred C57BL, Mice, Knockout, Models, Genetic, Spermatozoa |
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 Ca(2+) ionophore induces fertilizing capacity in sperm from infertile CatSper1 (Ca(2+) 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. |
DOI | 10.1038/srep33589 |
Alternate Journal | Sci Rep |
PubMed ID | 27627854 |
PubMed Central ID | PMC5024339 |
Grant List | R01 HD044044 / HD / NICHD NIH HHS / United States R01 HD051872 / HD / NICHD NIH HHS / United States R01 GM107442 / GM / NIGMS NIH HHS / United States R03 HD073523 / HD / NICHD NIH HHS / United States R01 HD038082 / HD / NICHD NIH HHS / United States R01 HD069631 / HD / NICHD NIH HHS / United States R01 HD059913 / HD / NICHD NIH HHS / United States R21 HD078942 / HD / NICHD NIH HHS / United States |