title: Dialkyl phosphate urinary metabolites and chromosomal abnormalities in human sperm.
abstract: BACKGROUND
  The past decade has seen numerous human health studies seeking to characterize the impacts of environmental exposures, such as organophosphate (OP) insecticides, on male reproduction. Despite an extensive literature on OP toxicology, many hormone-mediated effects on the testes are not well understood.
  
  
  OBJECTIVE
  This study investigated environmental exposures to OPs and their association with the frequency of sperm chromosomal abnormalities (i.e., disomy) among adult men.
  
  
  METHODS
  Men (n=159) from a study assessing the impact of environmental exposures on male reproductive health were included in this investigation. Multi-probe fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine XX18, YY18, XY18 and total disomy in sperm nuclei. Urine was analyzed using gas chromatography coupled with mass spectrometry for concentrations of dialkyl phosphate (DAP) metabolites of OPs [dimethylphosphate (DMP); dimethylthiophosphate (DMTP); dimethyldithiophosphate (DMDTP); diethylphosphate (DEP); diethylthiophosphate (DETP); and diethyldithiophosphate (DEDTP)]. Poisson regression was used to model the association between OP exposures and disomy measures. Incidence rate ratios (IRRs) were calculated for each disomy type by exposure quartiles for most metabolites, controlling for age, race, BMI, smoking, specific gravity, total sperm concentration, motility, and morphology.
  
  
  RESULTS
  A significant positive trend was seen for increasing IRRs by exposure quartiles of DMTP, DMDTP, DEP and DETP in XX18, YY18, XY18 and total disomy. A significant inverse association was observed between DMP and total disomy. Findings for total sum of DAP metabolites concealed individual associations as those results differed from the patterns observed for each individual metabolite. Dose-response relationships appeared nonmonotonic, with most of the increase in disomy rates occurring between the second and third exposure quartiles and without additional increases between the third and fourth exposure quartiles.
  
  
  CONCLUSIONS
  This is the first epidemiologic study of this size to examine the relationship between environmental OP exposures and human sperm disomy outcomes. Our findings suggest that increased disomy rates were associated with specific DAP metabolites, suggesting that the impacts of OPs on testis function need further characterization in epidemiologic studies.
authors.affiliation: Department of Environmental and Occupational Health, George Washington University, Milken Institute School of Public Health, 950 New Hampshire Ave. NW (4th Floor), Washington, DC 20052, United States. Electronic address: zfiguero@gwu.edu.
authors.forename: Zaida I
authors.initials: ZI
authors.lastname: Figueroa
authors.affiliation: Department of Epidemiology and Biostatistics, George Washington University, Milken Institute School of Public Health, 950 New Hampshire Ave. NW (5th Floor), Washington, DC 20052, United States. Electronic address: youngh@gwu.edu.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Young
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109-2029, United States. Electronic address: meekerj@umich.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
authors.affiliation: Department of Environmental and Occupational Health, George Washington University, Milken Institute School of Public Health, 950 New Hampshire Ave. NW (4th Floor), Washington, DC 20052, United States. Electronic address: smarten@umich.edu.
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Martenies
authors.affiliation: Department of Environmental Health, Emory University, Rollins School of Public Health, 1518 Clifton Road, NE, Atlanta, GA 30322, United States. Electronic address: dbbarr@emory.edu.
authors.forename: Dana Boyd
authors.initials: DB
authors.lastname: Barr
authors.affiliation: Department of Environmental and Occupational Health, George Washington University, Milken Institute School of Public Health, 950 New Hampshire Ave. NW (4th Floor), Washington, DC 20052, United States. Electronic address: gmgray@gwu.edu.
authors.forename: George
authors.initials: G
authors.lastname: Gray
authors.affiliation: Department of Environmental and Occupational Health, George Washington University, Milken Institute School of Public Health, 950 New Hampshire Ave. NW (4th Floor), Washington, DC 20052, United States. Electronic address: mperry@gwu.edu.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Perry
mesh_terms: D000328:Adult; D052244:Endocrine Disruptors / Q000378:metabolism / Q000652:urine*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000652:urine*; D016012:Poisson Distribution; D012729:Sex Chromosome Aberrations / Q000139:chemically induced* / Q000706:statistics & numerical data; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology; D011795:Surveys and Questionnaires; D024182:Uniparental Disomy / Q000139:chemically induced; D055815:Young Adult
chemical_list: D052244:Endocrine Disruptors; D009943:Organophosphorus Compounds
keywords: Aneuploidy; Endocrine disruptors; In situ hybridization; Organophosphate pesticides; Reproduction