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Human Reproduction, Vol. 17, No. 7, 1820-1825, July 2002
© 2002 European Society of Human Reproduction and Embryology

Sperm DNA damage in potentially fertile homozygous ß-thalassaemia patients with iron overload

Doreen Perera1, Arnold Pizzey2, Alastair Campbell3, Maurice Katz1, John Porter2, Mary Petrou1, D.S. Irvine3 and Ratna Chatterjee1,4

1 Departments of Obstetrics and Gynaecology and 2 Haematology, UCL London and 3 MRC Reproductive Biology Unit, Edinburgh, UK

BACKGROUND: To test the hypothesis that human sperm DNA could sustain iron-induced oxidative damage and reduce its fertilizing ability, we studied patients with homozygous ß-thalassaemia major (HbTh) as a model of iron overload. METHODS: 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. RESULTS: All patients with HbTh were iron overloaded (median ferritin: 2251 µg/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 (R2 = 0.80, P = 0.016) and TUNEL data (R2 = 0.67, P < 0.044). No other biochemical or clinical data were associated with sperm DNA damage. CONCLUSIONS: 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.

Key words: ß-thalassaemia/DNA damage/iron overload/oxidative stress/sperm

4 To whom correspondence should be addressed at: Reproductive Medicine Unit, Elizabeth Garret Anderson Hospital, iversity College Hospital, Huntley Street, London WC 1E 6AU, UK. E-mail: ratnach{at}globalnet.co.uk


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