title: Deficiency in mouse Y chromosome long arm gene complement is associated with sperm DNA damage.
abstract: BACKGROUND
  Mice with severe non-PAR Y chromosome long arm (NPYq) deficiencies are infertile in vivo and in vitro. We have previously shown that sperm from these males, although having grossly malformed heads, were able to fertilize oocytes via intracytoplasmic sperm injection (ICSI) and yield live offspring. However, in continuing ICSI trials we noted a reduced efficiency when cryopreserved sperm were used and with epididymal sperm as compared to testicular sperm. In the present study we tested if NPYq deficiency is associated with sperm DNA damage - a known cause of poor ICSI success.
  
  
  RESULTS
  We observed that epididymal sperm from mice with severe NPYq deficiency (that is, deletion of nine-tenths or the entire NPYq gene complement) are impaired in oocyte activation ability following ICSI and there is an increased incidence of oocyte arrest and paternal chromosome breaks. Comet assays revealed increased DNA damage in both epididymal and testicular sperm from these mice, with epididymal sperm more severely affected. In all mice the level of DNA damage was increased by freezing. Epididymal sperm from mice with severe NPYq deficiencies also suffered from impaired membrane integrity and abnormal chromatin condensation and suboptimal chromatin protamination. It is therefore likely that the increased DNA damage associated with NPYq deficiency is a consequence of disturbed chromatin remodeling.
  
  
  CONCLUSIONS
  This study provides the first evidence of DNA damage in sperm from mice with NPYq deficiencies and indicates that NPYq-encoded gene/s may play a role in processes regulating chromatin remodeling and thus in maintaining DNA integrity in sperm.
authors.affiliation: Institute for Biogenesis Research, John A Burns School of Medicine, University of Hawaii, 1960 East-West Rd, Honolulu, HI 96822, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Riel
authors.forename: Zoia
authors.initials: Z
authors.lastname: Stoytcheva
authors.forename: Paul S
authors.initials: PS
authors.lastname: Burgoyne
authors.forename: Monika A
authors.initials: MA
authors.lastname: Ward
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D033481:Chromosomes, Mammalian / Q000235:genetics* / Q000378:metabolism; D020552:Comet Assay; D015925:Cryopreservation; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D004822:Epididymis / Q000378:metabolism; D005260:Female; D005615:Freezing; D050173:Genes, Y-Linked / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D011479:Protamines / Q000378:metabolism; D020554:Sperm Injections, Intracytoplasmic; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D002843:Chromatin; D009687:Nuclear Proteins; D011479:Protamines