title: Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility.
abstract: OBJECTIVE
  To evaluate ejaculated spermatozoa from patients with male factor infertility for the role of cytochrome c and caspases 9 and 3 (the proteins known to mediate apoptosis) and to examine association between semen quality and apoptosis in the presence of oxidative stress.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  Male infertility clinic at a tertiary health care center.
  
  
  METHODS
  Semen specimens from 35 patients with idiopathic infertility and 8 normal healthy donors.
  
  
  METHODS
  Levels of ROS, cytochrome c, and caspases 9 and 3 and semen variables.
  
  
  RESULTS
  Compared with normal donors, infertile patients had significantly higher levels (expressed as median [25th and 75th percentiles]) of ROS (4.15 x 10(6) counted photons per minute [cpm] [0.26, 40.16 x 10(6) cpm] vs. 0.06 x 10(6) cpm [0.02, 0.29 x 10(6) cpm]; P<.01), cytochrome c (2.78 [2.21, 43.65 vs. 1.5 [1.25, 2.2]; P<.01)], caspase 9 (2.52 [0.9, 4.28] vs. 6 [4.85, 7.63]; P<.006), and caspase 3 (0.56 [0.32, 1.02] vs. 1.69 [1.66, 2.67]; P<.01). Semen variables (motility, concentration, and morphology) were negatively correlated with caspase 9 and 3 (P<.05). Reactive oxygen species was positively correlated with cytochrome c (r=.43; P<.03), caspase 9 (r=.56; P<.001), and caspase 3 (r=.65;P<.01).
  
  
  CONCLUSIONS
  Infertile men have decreased sperm variables induced by higher ROS levels in semen. A positive relationship exists between increased sperm damage by ROS and higher levels of cytochrome c and caspases 9 and 3, which indicate positive apoptosis in patients with male factor infertility.
authors.affiliation: Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Department of Obsterics and Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Sikka
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Thomas
authors.forename: Tommaso
authors.initials: T
authors.lastname: Falcone
authors.forename: Ashok
authors.initials: A
authors.lastname: Agarwal
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology
chemical_list: D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases