Hum. Reprod. Advance Access originally published online on November 7, 2006
Human Reproduction 2007 22(3):688-695; doi:10.1093/humrep/del428
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DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites
1 Department of Environmental Health, Harvard School of Public Health 2 Vincent Memorial Obstetrics & Gynecology Service, Andrology Laboratory and In Vitro Fertilization Unit, Massachusetts General Hospital, Boston, MA 3 Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 4 Department of Bioengineering, University of Washington, Seattle, WA 5 National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 6 Department of Biostatistics, Harvard School of Public Health and 7 Department of Nursing, School for Health Studies, Simmons College, Boston, MA, USA
8 To whom correspondence should be addressed at: Department of Environmental Health, Harvard School of Public Health, Occupational Health Program, Building 1, Room 1405, 665 Huntington Avenue, Boston, MA 02115, USA. E-mail: rhauser{at}hohp.harvard.edu
BACKGROUND: The ubiquitous use of phthalate esters in plastics, personal care products and food packaging materials results in widespread general population exposure. In this report, we extend our preliminary study on the relationship between urinary concentrations of phthalate metabolites and sperm DNA damage among a larger sample of men and include measurements of mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), two oxidative metabolites of di-(2-ethylhexyl) phthalate (DEHP). METHODS: Among 379 men from an infertility clinic, urinary concentrations of phthalate metabolites were measured using isotope-dilution high-performance liquid chromatography–tandem mass spectrometry. Sperm DNA damage measurements, assessed with the neutral comet assay, included comet extent (CE), percentage of DNA in tail (Tail%) and tail distributed moment (TDM). RESULTS: Monoethyl phthalate (MEP), a metabolite of diethyl phthalate, was associated with increased DNA damage, confirming our previous findings. Mono-(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP, was associated with DNA damage after adjustment for the oxidative DEHP metabolites. After adjustment for MEHHP, for an interquartile range increase in urinary MEHP, CE increased 17.3% [95% confidence interval (CI) = 8.7–25.7%], TDM increased 14.3% (95% CI = 6.8–21.7%) and Tail% increased 17.5% (95% CI = 3.5–31.5%). CONCLUSIONS: Sperm DNA damage was associated with MEP and with MEHP after adjusting for DEHP oxidative metabolites, which may serve as phenotypic markers of DEHP metabolism to ‘less toxic’ metabolites. The urinary levels of phthalate metabolites among these men were similar to those reported for the US general population, suggesting that exposure to some phthalates may affect the population distribution of sperm DNA damage.
Key words: phthalates/urinary metabolites/DNA damage/comet assay/human sperm
Submitted on July 14, 2006; resubmitted on September 28, 2006; accepted on October 5, 2006.
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