title: Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N mice.
abstract: BACKGROUND
  Di(2-ethylhexyl) phthalate (DEHP) and its metabolites are known to affect lipid metabolism and adipogenesis, mainly by activation of peroxisome proliferator-activated receptors (PPARs). Exposure to DEHP has been linked with testicular impairment and male subfertility. However, the effects of DEHP on female reproductive health and metabolism have not been studied in detail.
  
  
  OBJECTIVE
  We examined the effects of dietary DEHP exposure on metabolism and fertility in female mice.
  
  
  METHODS
  In two independent approaches, female C3H/N mice were exposed to DEHP (0.05, 5, or 500 mg/kg of body weight per day) via their diet for 8 weeks, and we recorded food intake, weight gain, and litter size. After exposure, liver, visceral fat, and plasma from F0 females (study I) and F0 dams and their F1 offspring (study II) were analyzed by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay.
  
  
  RESULTS
  In study I, DEHP-exposed F0 females (all dose groups) had a significant increase in body weight, food intake, and visceral adipose tissue compared with controls. In the 500-mg DEHP group, PPARα and PPARγ transcripts were significantly changed in liver tissue. In the same group, PPARγ mRNA was significantly reduced in liver but not in fat tissue. In addition, leptin and FABP4 (fatty acid binding protein 4) mRNA were increased in adipose tissue, whereas adiponectin was decreased. In study II, we detected a 100% abortion rate in F0 dams in the 500-mg group. F1 offspring exposed in utero and during lactation had an increase in visceral fat tissue and body weight.
  
  
  CONCLUSIONS
  Fertility was impaired in mice exposed to high doses of DEHP, and body weight and visceral fat deposits were increased in mice exposed to environmentally relevant doses. Although F1 mice were exposed to DEHP only in utero and during lactation, we observed metabolic changes in the offspring of diet-exposed females.
authors.affiliation: Department of Anatomy and Cell Biology, Martin Luther University Faculty of Medicine, Halle (Saale), Germany. juliane-susanne.schmidt@medizin.uni-halle.de
authors.forename: Juliane-Susanne
authors.initials: JS
authors.lastname: Schmidt
authors.forename: Kristina
authors.initials: K
authors.lastname: Schaedlich
authors.forename: Nadia
authors.initials: N
authors.lastname: Fiandanese
authors.forename: Paola
authors.initials: P
authors.lastname: Pocar
authors.forename: Bernd
authors.initials: B
authors.lastname: Fischer
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001483:Base Sequence; D001835:Body Weight; D017931:DNA Primers; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005247:Feeding Behavior; D005260:Female; D005298:Fertility / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D004051:Diethylhexyl Phthalate