title: Caspase activation in human spermatozoa in response to physiological and pathological stimuli.
abstract: OBJECTIVE
  To investigate caspase activation in response to a variety of pathological and physiological stimuli in light of the fact that current research offers no clear consensus about caspase activation pathways in spermatozoa.
  
  
  METHODS
  A prospective, controlled study.
  
  
  METHODS
  Male infertility clinic, Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
  
  
  METHODS
  Fifteen healthy volunteers.
  
  
  METHODS
  Spermatozoa were exposed to [1] Fibroblast-associated (Fas) death receptor activation, [2] mitochondrial apoptosis induction using betulinic acid, [3] oxidative stress, and [4] prolonged incubation up to 3 hours without any external stimuli.
  
  
  METHODS
  Active caspases-1, -3, -8, and -9 were examined in human spermatozoa by flow cytometry using carboxyfluorescein derivatives.
  
  
  RESULTS
  Inducing Fas antibody did not result in any caspase activation. Conversely, betulinic acid significantly triggered caspase-9 and -3 activation. The application of oxidative stress and prolonged incubation (3 hours) failed to result in caspase activation.
  
  
  CONCLUSIONS
  These results suggest that Fas has no functional relevance in mediating caspase activation in human ejaculated spermatozoa. Although spermatozoal mitochondria are highly susceptible to specific agonists of apoptosis such as betulinic acid via caspase activation, oxidative stress-induced apoptosis appears to be caspase independent.
authors.affiliation: Department of Dermatology/Andrology Unit, University of Leipzig, Leipzig, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Grunewald
authors.forename: Uwe
authors.initials: U
authors.lastname: Paasch
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Said
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Glander
authors.forename: Ashok
authors.initials: A
authors.lastname: Agarwal
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D053978:Pentacyclic Triterpenes; D011446:Prospective Studies; D013094:Spermatozoa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D014315:Triterpenes / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D020170:Caspase 1; D000094062:Betulinic Acid