title: In utero exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate promotes local adipose and systemic inflammation in adult male offspring.
abstract: BACKGROUND
  Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer used to increase the flexibility of polyvinyl chloride. DEHP and its active metabolite mono-(2-ethylhexyl) phthalate are detected in many biological fluids during fetal and postnatal life. In rodent models, in utero DEHP exposure has been shown to alter sexual organ development, decrease testosterone and aldosterone production, increase body and epididymal adipose tissue weight, and raise serum lipids and glucose levels in male offspring.
  
  
  OBJECTIVE
  The objective of this study is to characterize the effects of in utero DEHP exposure on adipose tissue development and function in male offspring.
  
  
  METHODS
  Sprague-Dawley pregnant dams were gavaged 1, 20, 50 or 300 mg DEHP per kg per day from gestational day 14 until birth.
  
  
  RESULTS
  Global gene expression analyses of postnatal day 60 male offspring that were exposed in utero to 300 mg DEHP per kg per day revealed increased expression of immune response and inflammation markers, and increased expression of differentiation pathway genes in the epididymal whole-adipose tissue and isolated stromal vascular fraction. C-reactive protein and tumor necrosis factor (TNF) serum levels were increased in the 300 mg DEHP in utero-exposed offspring. TNF levels in adipose tissue homogenates were increased in the 50 and 300 mg DEHP in utero-exposed offspring. Immunofluorescence studies revealed focal macrophage infiltration in whole-adipose tissue confirmed by increased CD163 tissue content.
  
  
  CONCLUSIONS
  In utero DEHP exposure promotes local adipose tissue inflammation and chronic low-grade systemic inflammation. Moreover, evidence is presented, suggesting that DEHP increases the differentiation capacity of the pre-adipocytes of male offspring without affecting total body weight.
authors.affiliation: 1] Research Institute of the McGill University Health Centre, Montreal General Hospital, Montréal, QC, Canada [2] Department of Medicine, McGill University, Montréal, QC, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Campioli
authors.affiliation: 1] Research Institute of the McGill University Health Centre, Montreal General Hospital, Montréal, QC, Canada [2] Department of Medicine, McGill University, Montréal, QC, Canada.
authors.forename: D B
authors.initials: DB
authors.lastname: Martinez-Arguelles
authors.affiliation: 1] Research Institute of the McGill University Health Centre, Montreal General Hospital, Montréal, QC, Canada [2] Department of Medicine, McGill University, Montréal, QC, Canada [3] Department of Biochemistry, McGill University, Montréal, QC, Canada [4] Department of Pharmacology and Therapeutics, McGill University, Montréal, QC, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Papadopoulos