title: Human sperm sex chromosome disomy and sperm DNA damage assessed by the neutral comet assay.
abstract: OBJECTIVE
  Is there an association between human sperm sex chromosome disomy and sperm DNA damage?
  
  
  CONCLUSIONS
  An increase in human sperm XY disomy was associated with higher comet extent; however, there was no other consistent association of sex chromosome disomies with DNA damage.
  
  
  BACKGROUND
  There is limited published research on the association between sex chromosome disomy and sperm DNA damage and the findings are not consistent across studies.
  
  
  METHODS
  We conducted a cross-sectional study of 190 men (25% ever smoker, 75% never smoker) from subfertile couples presenting at the Massachusetts General Hospital Fertility Clinic from January 2000 to May 2003.
  
  
  METHODS
  Multiprobe fluorescence in situ hybridization for chromosomes X, Y and 18 was used to determine XX, YY, XY and total sex chromosome disomy in sperm nuclei using an automated scoring method. The neutral comet assay was used to measure sperm DNA damage, as reflected by comet extent, percentage DNA in the comet tail, and tail distributed moment. Univariate and multiple linear regression models were constructed with sex chromosome disomy (separate models for each of the four disomic conditions) as the independent variable, and DNA damage parameters (separate models for each measure of DNA damage) as the dependent variable.
  
  
  RESULTS
  Men with current or past smoking history had significantly greater comet extent (µm: regression coefficients with 95% CI) [XX18: 15.17 (1.98, 28.36); YY18: 14.68 (1.50, 27.86); XY18: 15.41 (2.37, 28.45); Total Sex Chromosome Disomy: 15.23 (2.09, 28.38)], and tail distributed moment [XX18: 3.01 (0.30, 5.72); YY18: 2.95 (0.24, 5.67); XY18: 3.04 (0.36, 5.72); Total Sex Chromosome Disomy: 3.10 (0.31, 5.71)] than men who had never smoked. In regression models adjusted for age and smoking, there was a positive association between XY disomy and comet extent. For an increase in XY disomy from 0.56 to 1.47% (representing the 25th to 75th percentile), there was a mean increase of 5.08 µm in comet extent. No other statistically significant findings were observed.
  
  
  CONCLUSIONS
  A potential limitation of this study is that it is cross-sectional. Cross-sectional analyses by nature do not lend themselves to inference about directionality for any observed associations; therefore we cannot determine which variable is the cause and which one is the effect. A small sample size may be a further limitation. Comparison of these findings to other studies is limited due to methodological differences.
  
  
  CONCLUSIONS
  Although consistent associations across sex chromosome disomies or DNA damage measures were not observed, this study highlights the need to explore etiologies of sperm DNA damage and sex chromosome disomy to better understand the potential mechanistic overlaps between the two.
  
  
  BACKGROUND
  This work was supported by NIOSH Grant T42 OH008416, and NIH/NIEHS Grants ES 009718, ES 000002, and R01 ES017457. During the study M.E.M. was affiliated with the Department of Environmental Health at the Harvard School of Public Health.
  
  
  BACKGROUND
  N/A.
authors: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA Millennium: The Takeda Oncology Company, Cambridge, MA 02139, USA.
authors: M E
authors: ME
authors: McAuliffe
authors: Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors: P L
authors: PL
authors: Williams
authors: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: S A
authors: SA
authors: Korrick
authors: Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
authors: R
authors: R
authors: Dadd
authors: Environmental Health Science Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.
authors: F
authors: F
authors: Marchetti
authors: Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA.
authors: S E
authors: SE
authors: Martenies
authors: Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA mperry@gwu.edu.
authors: M J
authors: MJ
authors: Perry
mesh_terms: D000328:Adult; D000782:Aneuploidy; D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D020552:Comet Assay; D003430:Cross-Sectional Studies; D004249:DNA Damage; D053938:DNA Fragmentation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D012044:Regression Analysis; D055101:Semen Analysis; D012729:Sex Chromosome Aberrations; D012907:Smoking; D013094:Spermatozoa
keywords: DNA damage; aneuploidy; fluorescence in situ hybridization; neutral comet assay; semen