title: Sperm DNA damage in potentially fertile homozygous beta-thalassaemia patients with iron overload.
abstract: 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 beta-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 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.
  
  
  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.
authors.affiliation: Department of Obstetrics and Gynaecology, University College Hospital, UCL London, Huntley Street, London WC1E 6AU, UK.
authors.forename: Doreen
authors.initials: D
authors.lastname: Perera
authors.forename: Arnold
authors.initials: A
authors.lastname: Pizzey
authors.forename: Alastair
authors.initials: A
authors.lastname: Campbell
authors.forename: Maurice
authors.initials: M
authors.lastname: Katz
authors.forename: John
authors.initials: J
authors.lastname: Porter
authors.forename: Mary
authors.initials: M
authors.lastname: Petrou
authors.forename: D S
authors.initials: DS
authors.lastname: Irvine
authors.forename: Ratna
authors.initials: R
authors.lastname: Chatterjee
mesh_terms: D000328:Adult; D004249:DNA Damage; D005298:Fertility; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000150:complications*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D013081:Sperm Motility; D013094:Spermatozoa / Q000502:physiology*; D017086:beta-Thalassemia / Q000150:complications* / Q000503:physiopathology*