Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes.
Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health.
Agarwal
Ashok
A
Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA. agarwaa@ccf.org
Mahfouz
Reda Z
RZ
Sharma
Rakesh K
RK
Sarkar
Oli
O
Mangrola
Devna
D
Mathur
Premendu P
PP
D000328:Adult; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D002843:Chromatin / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D005298:Fertility / Q000502:physiology; D005819:Genetic Markers; D006801:Humans; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000201:enzymology* / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology
D002843:Chromatin; D005819:Genetic Markers; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases