PMID- 26519831 OWN - NLM STAT- MEDLINE DCOM- 20160229 LR - 20181113 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 143 IP - Pt A DP - 2015 Nov TI - Dialkyl phosphate urinary metabolites and chromosomal abnormalities in human sperm. PG - 256-65 LID - S0013-9351(15)30119-5 [pii] LID - 10.1016/j.envres.2015.10.021 [doi] AB - 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. OBJECTIVES: 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Figueroa, Zaida I AU - Figueroa ZI AD - 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. FAU - Young, Heather A AU - Young HA AD - 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. FAU - Meeker, John D AU - Meeker JD AD - 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. FAU - Martenies, Sheena E AU - Martenies SE AD - 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. FAU - Barr, Dana Boyd AU - Barr DB AD - 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. FAU - Gray, George AU - Gray G AD - 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. FAU - Perry, Melissa J AU - Perry MJ AD - 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. LA - eng GR - R01 ES017457/ES/NIEHS NIH HHS/United States GR - P30 ES000002/ES/NIEHS NIH HHS/United States GR - ES 009718/ES/NIEHS NIH HHS/United States GR - R01 ES009718/ES/NIEHS NIH HHS/United States GR - R01ES017457/ES/NIEHS NIH HHS/United States GR - ES000002/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20151028 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 0 (Endocrine Disruptors) RN - 0 (Organophosphorus Compounds) SB - IM MH - Adult MH - Endocrine Disruptors/metabolism/*urine MH - Environmental Exposure/*adverse effects/analysis MH - Gas Chromatography-Mass Spectrometry MH - Humans MH - In Situ Hybridization, Fluorescence MH - Limit of Detection MH - Male MH - Middle Aged MH - Organophosphorus Compounds/metabolism/*urine MH - Poisson Distribution MH - Sex Chromosome Aberrations/*chemically induced/statistics & numerical data MH - Spermatozoa/*drug effects/pathology MH - Surveys and Questionnaires MH - Uniparental Disomy/chemically induced MH - Young Adult PMC - PMC4743645 MID - NIHMS734290 OTO - NOTNLM OT - Aneuploidy OT - Endocrine disruptors OT - In situ hybridization OT - Organophosphate pesticides OT - Reproduction EDAT- 2015/11/01 06:00 MHDA- 2016/03/02 06:00 PMCR- 2016/11/01 CRDT- 2015/11/01 06:00 PHST- 2015/08/06 00:00 [received] PHST- 2015/10/16 00:00 [revised] PHST- 2015/10/19 00:00 [accepted] PHST- 2015/11/01 06:00 [entrez] PHST- 2015/11/01 06:00 [pubmed] PHST- 2016/03/02 06:00 [medline] PHST- 2016/11/01 00:00 [pmc-release] AID - S0013-9351(15)30119-5 [pii] AID - 10.1016/j.envres.2015.10.021 [doi] PST - ppublish SO - Environ Res. 2015 Nov;143(Pt A):256-65. doi: 10.1016/j.envres.2015.10.021. Epub 2015 Oct 28.