Impact of sperm morphology on DNA damage caused by oxidative stress induced by beta-nicotinamide adenine dinucleotide phosphate.
OBJECTIVE
To investigate the role of DNA damage induced by beta-nicotinamide adenine dinucleotide phosphate (NADPH) in human spermatozoa.


METHODS
Prospective controlled study.


METHODS
Male infertility clinic at the Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio.


METHODS
Twenty-eight men undergoing infertility screening.


METHODS
Chemiluminescence assay and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) assay coupled flow cytometry after incubating mature and immature sperm separated by density gradient with 5 mM NADPH for 0, 3, and 24 hours.


METHODS
Reactive oxygen species (ROS) generation (10(6) counted photons per minute/10(6) sperm) and percentage of spermatozoa with fragmented DNA.


RESULTS
Immature sperm from teratozoospermic semen samples were characterized by a statistically significant presence of cytoplasmic residues in the mid-piece when compared with mature normozoospermic samples. Increased ROS production was observed in spermatozoa rich in cytoplasmic residues that showed a statistically significant positive correlation with sperm DNA damage in a time-dependent manner.


CONCLUSIONS
Immature sperm contain high nicotinamide adenine dinucleotide phosphate (NADPH) in cytoplasmic droplets, but it has not yet been clear whether abnormal sperm morphology plays any role in sperm DNA damage induced by oxidative stress. Our data support the role of NAPDH in ROS-mediated sperm DNA damage and suggest that abnormal sperm morphology combined with elevated ROS production may serve as a useful indicator of potential damage to sperm DNA.
Said
Tamer M
TM
Center for Advanced Research in Human Reproduction, Infertility and Sexual Function, The Cleveland Clinic Foundation, Ohio 44195, USA.
Agarwal
Ashok
A
Sharma
Rakesh K
RK
Thomas
Anthony J
AJ
Sikka
Suresh C
SC
D004249:DNA Damage; D006801:Humans; D008297:Male; D009249:NADP / Q000633:toxicity*; D018384:Oxidative Stress; D011446:Prospective Studies; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology*
D009249:NADP