title: Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints.
abstract: BACKGROUND
  Brominated flame retardants (BFRs) are endocrine disruptors that bioaccumulate in the placenta, but it remains unclear if they disrupt tissue thyroid hormone (TH) metabolism. Our primary goal was to investigate associations between placental BFRs, TH levels, Type 3 deiodinase (DIO3) activity and TH sulfotransferase (SULT) activities.
  
  
  METHODS
  Placenta samples collected from 95 women who delivered term (>37 weeks) infants in Durham, NC, USA (enrolled 2010-2011) were analyzed for polybrominated diphenyl ethers (PBDEs), 2,4,6-tribromophenol (2,4,6-TBP), THs (T4, T3 and rT3), and DIO3 and TH SULT activities.
  
  
  RESULTS
  PBDEs and 2,4,6-TBP were detected in all placenta samples. PBDEs were higher in placental tissues from male infants compared to female infants, with 2,4,6-TBP and BDE-209 levels approximately twice as high. Among male infants, placental BDE-99 and BDE-209 were negatively associated with rT3 placental levels. For female infants, placental BDE-99 and 2,4,6-TBP were positively associated with T3 concentrations. DIO3 activity was also significantly higher in placental tissues from male infants compared to females, while 3,3'-T2 SULT activity was significantly higher in placental tissues from females compared to males. Among males, several PBDE congeners were positively correlated with T3 SULT, while BDE-99 was negatively associated with T3 SULT among females. Associations generally remained after adjustment for potential confounding by maternal age and gestational age at delivery.
  
  
  CONCLUSIONS
  These results suggest BFRs accumulate in the placenta and potentially alter TH function in a sex-specific manner, a possible mechanism to explain the sex-dependent impacts of environmental exposure on children's growth and development. More research is needed to elucidate the effects of BFRs on placenta function during pregnancy, as well as the biological consequences of exposure and thyroid disruption.
authors.affiliation: Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Leonetti
authors.affiliation: Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Butt
authors.affiliation: Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: Hoffman
authors.affiliation: Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Hammel
authors.affiliation: Department of Statistics, Rice University, Houston, TX, USA.
authors.forename: Marie Lynn
authors.initials: ML
authors.lastname: Miranda
authors.affiliation: Nicholas School of the Environment, Duke University, 9 Circuit Drive, Box 90328, Durham, NC, 27708, USA. heather.stapleton@duke.edu.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Stapleton
mesh_terms: D000328:Adult; D052244:Endocrine Disruptors / Q000032:analysis* / Q000097:blood; D005260:Female; D005411:Flame Retardants / Q000032:analysis*; D055768:Halogenated Diphenyl Ethers / Q000032:analysis* / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000032:analysis* / Q000097:blood; D010920:Placenta / Q000737:chemistry*; D011247:Pregnancy; D015238:Sulfotransferases / Q000378:metabolism; D013974:Thyroxine / Q000032:analysis; D014284:Triiodothyronine / Q000032:analysis
chemical_list: D052244:Endocrine Disruptors; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D010636:Phenols; D014284:Triiodothyronine; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase; D015238:Sulfotransferases; D013974:Thyroxine; C004554:2,4,6-tribromophenol
keywords: 2,4,6-tribromophenol (2,4,6-TBP); Placenta; Polybrominated diphenyl ether (PBDE); Thyroid hormone