Perera Doreen, Pizzey Arnold, Campbell Alastair, Katz Maurice, Porter John, Petrou Mary, Irvine D S, Chatterjee Ratna
Department of Obstetrics and Gynaecology, University College Hospital, UCL London, Huntley Street, London WC1E 6AU, UK.
Hum Reprod. 2002 Jul;17(7):1820-5. doi: 10.1093/humrep/17.7.1820.
To test the hypothesis that human sperm DNA could sustain iron-induced oxidative damage and reduce its fertilizing ability, we studied patients with homozygous beta-thalassaemia major (HbTh) as a model of iron overload.
Sperm from six thalassaemic patients and five age-matched controls were assessed by the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay. Semen parameters, endocrine markers of testicular function, iron profiles and the presence of organ dysfunction were also determined.
All patients with HbTh were iron overloaded (median ferritin: 2251 microg/l) and had evidence of spontaneous spermatogenesis. Thalassaemic patients had more sperm DNA damage than the controls (P < 0.01). The sperm DNA damage by SCSA and TUNEL were positively correlated (P < 0.05). Sperm motility and TUNEL results were negatively correlated (P < 0.05), while the age of onset of chelation and sperm DNA damage were positively associated with both SCSA (R(2) = 0.80, P = 0.016) and TUNEL data (R(2) = 0.67, P < 0.044). No other biochemical or clinical data were associated with sperm DNA damage.
The increase in sperm DNA damage and the negative correlation between sperm motility and DNA damage suggest that iron overload in HbTh predisposes sperm to oxidative injury. This finding has important implications in assisted reproductive procedures such as ICSI where there is increased risk of transmitting defective DNA to the offspring.
为验证人类精子DNA是否会遭受铁诱导的氧化损伤并降低其受精能力这一假说，我们以重型纯合子β地中海贫血（HbTh）患者作为铁过载模型展开研究。
采用精子染色质结构分析（SCSA）和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）分析，对6例地中海贫血患者及5例年龄匹配的对照者的精子进行评估。同时还测定了精液参数、睾丸功能的内分泌标志物、铁代谢指标以及器官功能障碍情况。
所有HbTh患者均存在铁过载（中位铁蛋白：2251μg/l）且有自发精子发生的证据。地中海贫血患者的精子DNA损伤比对照组更多（P<0.01）。SCSA和TUNEL检测的精子DNA损伤呈正相关（P<0.05）。精子活力与TUNEL结果呈负相关（P<0.05），而螯合治疗开始年龄及精子DNA损伤与SCSA（R² = 0.80，P = 0.016）和TUNEL数据（R² = 0.67，P<0.044）均呈正相关。没有其他生化或临床数据与精子DNA损伤相关。
精子DNA损伤增加以及精子活力与DNA损伤之间的负相关表明，HbTh患者的铁过载使精子易发生氧化损伤。这一发现对诸如卵胞浆内单精子注射（ICSI）等辅助生殖程序具有重要意义，因为在这些程序中，将缺陷DNA传递给后代的风险会增加。
