title: Transient exposure to calcium ionophore enables in vitro fertilization in sterile mouse models.
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.
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Navarrete
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alvau
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Hoi Chang
authors.initials: HC
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Lonny R
authors.initials: LR
authors.lastname: Levin
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Buck
authors.affiliation: Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Patricia Martin-De
authors.initials: PM
authors.lastname: Leon
authors.affiliation: Department of Obstetrics and Gynecology, Basic Sciences Division, Washington University School of Medicine. St. Louis, MO, USA.
authors.forename: Celia M
authors.initials: CM
authors.lastname: Santi
authors.affiliation: Instituto de Biología Molecular y Celular de Rosario (CONICET-UNR), 2000 Rosario, Argentina.
authors.forename: Dario
authors.initials: D
authors.lastname: Krapf
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Mager
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Salicioni
authors.affiliation: Departamento de Genética del Desarrollo y Fisiología Molecular, IBT-UNAM, Cuernavaca, México.
authors.forename: Alberto
authors.initials: A
authors.lastname: Darszon
authors.affiliation: Department of Veterinary and Animal Science, Integrated Sciences Building, University of Massachusetts, Amherst MA, USA.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Visconti
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D061207:Calcium Ionophores / Q000494:pharmacology*; D004195:Disease Models, Animal; D005306:Fertilization / Q000187:drug effects; D005307:Fertilization in Vitro; D007248:Infertility, Male / Q000473:pathology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D013094:Spermatozoa / Q000187:drug effects
chemical_list: D015220:Calcium Channels; D061207:Calcium Ionophores; C488642:Catsper1 protein, mouse; C110627:Kcnu1 protein, mouse; D051036:Large-Conductance Calcium-Activated Potassium Channels; D000001:Calcimycin; D000262:Adenylyl Cyclases