title: Urinary phthalate and phthalate alternative metabolites and isoprostane among couples undergoing fertility treatment.
abstract: BACKGROUND
  Epidemiological data suggest associations between phthalate exposures to a variety of adverse reproductive outcomes including reduced sperm quality and reproductive success. While mechanisms of these associations are not fully elucidated, oxidative stress has been implicated as a potential mediator. We examined associations of urinary metabolites of phthalates and phthalate alternative plasticizers with oxidative stress among couples seeking fertility treatment.
  
  
  METHODS
  Seventeen urinary plasticizer metabolites and 15-F2t isoprostane, a biomarker of oxidative stress, were quantified in spot samples from 50 couples seeking fertility treatment who enrolled in the Sperm Environmental Epigenetics and Development Study during 2014-2015.
  
  
  RESULTS
  In multivariable analyses, percent change in isoprostane was positively associated with interquartile range increases for the oxidative metabolites of di-2-ethylhexyl phthalate, [mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP; 20.0%, p=0.02), mono-2-ethyl-5-oxohexyl phthalate (MEOHP; 24.1%, p=0.01), and mono-2-ethyl-5-carboxypentyl phthalate (MECPP; 24.1%, p=0.004)], mono-isobutyl phthalate (MiBP; 17.8%, p=0.02), mono-hydroxyisobutyl phthalate (MHiBP; 27.5%, p=0.003), and cyclohexane-1,2-dicarboxylic acid mono-hydroxy-isononyl ester (MHINCH; 32.3%, p=0.002). Stratification of participants by sex revealed that isoprostane was positively associated with MHiBP (41.4%, p=0.01) and monocarboxy-isononyl phthalate (MCNP; 26.0%, p=0.02) among females and MEOHP (35.8%, p=0.03), MiBP (29.2%, p=0.01), MHiBP (34.7%, p=0.007) and MHINCH (49.0%, p=0.002) among males.
  
  
  CONCLUSIONS
  Our results suggest that exposure to phthalates and phthalate replacements are associated with higher levels of oxidative stress in a sex-specific manner. Additional studies are needed to replicate our findings and to examine the potential health implications of the use of phthalates and alternative phthalates in consumer end products.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, United States.
authors.forename: Haotian
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, United States.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Olmsted
authors.affiliation: Department of Obstetrics Gynecology and Reproductive Biology, Division of Maternal Fetal Medicine Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Cantonwine
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, United States.
authors.forename: Shahin
authors.initials: S
authors.lastname: Shahsavari
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, United States.
authors.forename: Tayyab
authors.initials: T
authors.lastname: Rahil
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199, United States.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Sites
authors.affiliation: Department of Environmental Health Sciences, School of Public Health and Health Sciences, University of Massachusetts, 686 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: rpilsner@umass.edu.
authors.forename: J Richard
authors.initials: JR
authors.lastname: Pilsner
mesh_terms: D000293:Adolescent; D000328:Adult; D003430:Cross-Sectional Studies; D004051:Diethylhexyl Phthalate; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D005260:Female; D006801:Humans; D007246:Infertility / Q000209:etiology*; D028421:Isoprostanes / Q000652:urine*; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids / Q000378:metabolism / Q000652:urine*; D055815:Young Adult
chemical_list: D028421:Isoprostanes; D010795:Phthalic Acids; C479069:mono(2-ethyl-5-hydroxyhexyl) phthalate; C080276:mono(2-ethyl-5-oxohexyl)phthalate; C051450:2-ethyl-5-carboxypentyl phthalate; C032279:phthalic acid; D004051:Diethylhexyl Phthalate
keywords: EDC; Endocrine disruptors; Isoprostane; Oxidative stress; Phthalates