Brominated flame retardants in placental tissues: associations with infant sex and thyroid hormone endpoints

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.