Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility

Fertil Steril. 2003 Sep;80(3):531-5. doi: 10.1016/s0015-0282(03)00756-8.

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.

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 [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).

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.

MeSH terms

  • Apoptosis*
  • Caspase 3
  • Caspase 9
  • Caspases / metabolism
  • Cytochrome c Group / metabolism
  • DNA Damage*
  • Humans
  • Infertility, Male / genetics
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Infertility, Male / physiopathology*
  • Male
  • Oxidative Stress*
  • Prospective Studies
  • Reactive Oxygen Species / metabolism
  • Sperm Count
  • Sperm Motility
  • Spermatozoa* / metabolism
  • Spermatozoa* / pathology

Substances

  • Cytochrome c Group
  • Reactive Oxygen Species
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Caspases