Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility.
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.
Wang
Xia
X
Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Department of Obsterics and Gynecology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Sharma
Rakesh K
RK
Sikka
Suresh C
SC
Thomas
Anthony J
AJ
Falcone
Tommaso
T
Agarwal
Ashok
A
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
D003574:Cytochrome c Group; D017382:Reactive Oxygen Species; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases