Dialkyl phosphate urinary metabolites and chromosomal abnormalities in human sperm

• Type of Material: Article
• Authors: Zaida I. Figueroa, George Washington University; Heather A. Young, George Washington University; John D. Meeker, University of Michigan; Sheena E. Martenies, George Washington University; Dana Barr, Emory University; George Gray, George Washington University; Melissa J. Perry, George Washington University
• Language: English
• Date: 2015-11-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• License: Creative Commons Attribution-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.envres.2015.10.021
• Title of Journal or Parent Work: Environmental Research
• ISSN: 0013-9351
• Volume: 143
• Issue: Pt A
• Start Page: 256
• End Page: 265
• Grant/Funding Information: This work was supported by the following grants: ES 009718, ES 000002 and ES 017457.
• Keywords: Life Sciences & Biomedicine; Organophosphate pesticides; Endocrine disruptors; DNA-DAMAGE; Environmental Sciences; CREATININE EXCRETION; SEMEN QUALITY; Environmental Sciences & Ecology; Aneuploidy; In situ hybridization; ENVIRONMENTAL EXPOSURE; Public, Environmental & Occupational Health; Science & Technology; ESTROGENIC ACTIVITY; NONPERSISTENT INSECTICIDES; POLYCHLORINATED-BIPHENYLS; Reproduction; MEXICAN AGRICULTURAL-WORKERS
• Research Categories: Health Sciences, Epidemiology; Environmental Sciences; Health Sciences, Toxicology

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. 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.