Effect of Tetrabromobisphenol A on expression of biomarkers for inflammation and neurodevelopment by the placenta

Objective: Polybrominated diphenyl ethers (PBDEs) enhance basal and bacteria-stimulated production of proinflammatory cytokines by the placenta and may also increase the risk of preterm birth and neurodevelopmental disorders. Whether or not other brominated flame retardants such as Tetrabromobisphenol A (TBBPA) have similar properties is unclear. Therefore, we evaluated the effects of TBBPA on the production of steroids, as well as biomarkers for inflammation, oxidative stress, and neurodevelopment by the placenta. Methods: Placental explant cultures were established from women undergoing elective Cesarean sections at term and treated with 5–50,000 nM TBBPA in the presence and absence of 10 ⁷ CFU/ml heat-killed E. coli. Concentrations of P ₄ , E ₂ , testosterone (T), IL-1β, TNF-α, IL-10, HO-1, IL-6, 8-IsoP and BDNF were quantified in the conditioned medium. Results: In the absence of bacteria, TBBPA tended to increase P ₄ and T as well as IL-6 and 8-IsoP. For bacteria-treated cultures, TBBPA generally inhibited P ₄ , IL-1β, and HO-1 production but enhanced TNF-α and IL-6 production. Conclusions: TBBPA alters placental steroidogenesis to favor T production and increases oxidative stress and placental inflammation as suggested by its promotion of 8-IsoP and IL-6 production. TBBPA may also function as a risk modifier where it enhances bacteria-stimulated production TNF-α and IL-6 but reduces HO-1 production, however, this was balanced by reductions in IL-1β. Further studies are warranted to determine if TBBPA increases the risk of adverse pregnancy outcomes such as preterm birth, pPROM and neurodevelopmental disorders such as autism that have been associated with increased production of proinflammatory cytokines, oxidative stress and/or T.