Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

被引:123
作者
Agarwal, Ashok [1 ]
Mahfouz, Reda Z. [1 ]
Sharma, Rakesh K. [1 ]
Sarkar, Oli [2 ,3 ]
Mangrola, Devna [1 ]
Mathur, Premendu P. [2 ]
机构
[1] Cleveland Clin, Ctr Reprod Med, Cleveland, OH 44106 USA
[2] Pondicherry Univ, Dept Biochem & Mol Biol, Pondicherry, India
[3] McGill Univ, Ctr Hlth, Montreal, PQ, Canada
关键词
SPERM DNA-DAMAGE; RAT GERMINAL CELLS; BASE EXCISION-REPAIR; NF-KAPPA-B; HUMAN POLY(ADP-RIBOSE) POLYMERASE-1; EJACULATED HUMAN SPERMATOZOA; STRAND BREAK REPAIR; OXIDATIVE STRESS; MALE-INFERTILITY; CHROMATIN-STRUCTURE;
D O I
10.1186/1477-7827-7-143
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
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.
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页数:20
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