Tetrabromobisphenol A activates inflammatory pathways in human first trimester extravillous trophoblasts in vitro

• A brominated flame retardant activated proinflammatory response in placental cells.
• TBBPA stimulated cell release of the pro-inflammatory cytokines IL-6 and IL-8.
• TBBPA suppressed cell release of the anti-inflammatory cytokine TGF-β.
• TBBPA enhanced cyclooxygenase-2 (COX-2) mRNA expression and PGE2 production.
• We identified 7 genes differentially expressed with TBBPA exposure.

Tetrabromobisphenol A (TBBPA) is a widely used flame retardant. Despite the presence of TBBPA in gestational tissues and the importance of proper regulation of inflammatory networks for successful pregnancy, there is no prior study on the effects of TBBPA on inflammatory responses in gestational tissues. The present study aimed to investigate TBBPA activation of inflammatory pathways, specifically cytokine and prostaglandin production, in the human first trimester placental cell line HTR-8/SVneo. TBBPA enhanced release of interleukin (IL)-6, IL-8, and prostaglandin E2 (PGE2), and suppressed TGF-β release in HTR-8/SVneo cells. The lowest effective concentration was 10 μM TBBPA. A commercial immune response PCR array revealed increased expression of genes involved in inflammatory pathways stimulated by TBBPA in HTR-8/SVneo cells. Because proper regulation of inflammatory mediators in the gestational compartment is necessary for normal placental development and successful pregnancy, further investigation on the impact of TBBPA-stimulated responses on trophoblast function is warranted.