title: The opening of maitotoxin-sensitive calcium channels induces the acrosome reaction in human spermatozoa: differences from the zona pellucida.
abstract: The acrosome reaction (AR), an absolute requirement for spermatozoa and egg fusion, requires the influx of Ca²(+) into the spermatozoa through voltage-dependent Ca²(+) channels and store-operated channels. Maitotoxin (MTx), a Ca²(+)-mobilizing agent, has been shown to be a potent inducer of the mouse sperm AR, with a pharmacology similar to that of the zona pellucida (ZP), possibly suggesting a common pathway for both inducers. Using recombinant human ZP3 (rhZP3), mouse ZP and two MTx channel blockers (U73122 and U73343), we investigated and compared the MTx- and ZP-induced ARs in human and mouse spermatozoa. Herein, we report that MTx induced AR and elevated intracellular Ca²(+) ([Ca²(+)](i)) in human spermatozoa, both of which were blocked by U73122 and U73343. These two compounds also inhibited the MTx-induced AR in mouse spermatozoa. In disagreement with our previous proposal, the AR triggered by rhZP3 or mouse ZP was not blocked by U73343, indicating that in human and mouse spermatozoa, the AR induction by the physiological ligands or by MTx occurred through distinct pathways. U73122, but not U73343 (inactive analogue), can block phospholipase C (PLC). Another PLC inhibitor, edelfosine, also blocked the rhZP3- and ZP-induced ARs. These findings confirmed the participation of a PLC-dependent signalling pathway in human and mouse zona protein-induced AR. Notably, edelfosine also inhibited the MTx-induced mouse sperm AR but not that of the human, suggesting that toxin-induced AR is PLC-dependent in mice and PLC-independent in humans.
authors.affiliation: Department of Developmental Genetics and Molecular Physiology, Biotechnology Institute, UNAM, Cuernavaca, Mexico. ctrevino@ibt.unam.mx
authors.forename: Julio C
authors.initials: JC
authors.lastname: Chávez
authors.forename: Gerardo A
authors.initials: GA
authors.lastname: de Blas
authors.forename: José L
authors.initials: JL
authors.lastname: de la Vega-Beltrán
authors.forename: Takuya
authors.initials: T
authors.lastname: Nishigaki
authors.forename: Mayel
authors.initials: M
authors.lastname: Chirinos
authors.forename: María Elena
authors.initials: ME
authors.lastname: González-González
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: Alejandra
authors.initials: A
authors.lastname: Solís
authors.forename: Alberto
authors.initials: A
authors.lastname: Darszon
authors.forename: Claudia L
authors.initials: CL
authors.lastname: Treviño
mesh_terms: D020101:Acrosome Reaction / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D008297:Male; D008387:Marine Toxins / Q000494:pharmacology*; D051379:Mice; D035964:Oxocins / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013075:Sperm Capacitation / Q000502:physiology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D015044:Zona Pellucida / Q000187:drug effects / Q000378:metabolism*; D000095702:Polyether Toxins
chemical_list: D002118:Calcium; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004963:Estrenes; D008387:Marine Toxins; D035964:Oxocins; D011760:Pyrrolidinones; D010738:Type C Phospholipases; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074854:U 73343; C020394:maitotoxin; D000095702:Polyether Toxins