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. Design: Prospective study. Setting: Male infertility clinic at a tertiary health care center. Patient(s): Semen specimens from 35 patients with idiopathic infertility and 8 normal healthy donors. Main Outcome Measure(s): Levels of ROS, cytochrome c, and caspases 9 and 3 and semen variables. Result(s): Compared with normal donors, infertile patients had significantly higher levels (expressed as median [25(th) and 75(th) 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). Conclusion(s): 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. (C) 2003 by American Society for Reproductive Medicine.