Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Mol Reprod Dev. 2012 Sep;79(9):637-50. doi: 10.1002/mrd.22072. Epub 2012 Jul 31.
Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non-azoospermic men with intact Y chromosome (n = 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males.
男性不育是一种多因素疾病，确定个体的病因对于治疗至关重要。系统阐明导致精子 DNA 损伤的潜在遗传原因（染色体和 Yq 微缺失）和因素，如活性氧（ROS）水平和总抗氧化能力（TAC），可能有助于减少特发性不育男性的数量，并为他们提供最合适的治疗和咨询。本研究旨在全面调查可能导致大部分特发性不育男性病因的遗传和氧化应激因素。对 112 名不育男性和 76 名健康对照组进行了染色体异常和 Yq 微缺失筛查。对核型正常、非无精子症且 Y 染色体完整的男性（n=93）进行了 ROS、TAC 和精子 DNA 损伤评估。通过化学发光法评估未处理和洗涤精液中的 ROS；使用市售试剂盒评估精液 TAC；通过彗星试验评估精子 DNA 损伤。两名男性存在细胞遗传学异常，七名男性存在 Yq 微缺失。不育男性未处理和洗涤精液中的 ROS 水平明显高于对照组（P<0.01）。不育男性的 TAC 水平明显较低（P<0.01），而不育男性的精子 DNA 碎片化明显较高（P<0.01）。遗传因素和氧化应激共同导致了大量的特发性不育病例。与无法治愈的遗传原因不同，及时识别和管理氧化应激可能有助于逆转/减少对诱导性 DNA 损伤的影响，并改善不育男性的结局。
