Effect of Tetrabromobisphenol A on expression of biomarkers for inflammation and neurodevelopment by the placenta
Yuko Arita1, Matthew Pressman1, Darios Getahun2
1Department of Biomedical Research, Winthrop University Hospital, Mineola, NY 11501, USA.
Insights
Tetrabromobisphenol A (TBBPA) exposure alters placental steroid production and increases oxidative stress and inflammation. While TBBPA may modify bacterial-induced responses, its full impact on pregnancy outcomes requires further investigation.
Area of Science:
- Environmental Health
- Reproductive Toxicology
- Endocrinology
Background:
- Polybrominated diphenyl ethers (PBDEs) are linked to adverse pregnancy outcomes.
- The effects of other brominated flame retardants, like Tetrabromobisphenol A (TBBPA), on placental function are not well understood.
Purpose of the Study:
- To investigate the impact of TBBPA on placental production of steroids, inflammation, oxidative stress, and neurodevelopment biomarkers.
- To assess TBBPA's effects in both basal conditions and in the presence of bacterial stimulation.
Main Methods:
- Human placental explants from Cesarean sections were cultured.
- Explants were treated with varying concentrations of TBBPA, with or without heat-killed *E. coli*.
- Steroid hormones (P4, E2, T) and cytokine/biomarker levels (IL-1β, TNF-α, IL-10, HO-1, IL-6, 8-IsoP, BDNF) were quantified.
Main Results:
- TBBPA alone tended to increase progesterone (P4) and testosterone (T) production, along with IL-6 and 8-IsoP.
- In the presence of bacteria, TBBPA inhibited P4, IL-1β, and HO-1 but enhanced TNF-α and IL-6 production.
Conclusions:
- TBBPA alters placental steroidogenesis, favoring testosterone production.
- TBBPA appears to increase oxidative stress and inflammation, potentially modifying bacterial-induced inflammatory responses.
- Further research is needed to determine TBBPA's role in adverse pregnancy outcomes like preterm birth and neurodevelopmental disorders.
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 107 CFU/ml heat-killed E. coli. Concentrations of P4, E2, 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 P4 and T as well as IL-6 and 8-IsoP. For bacteria-treated cultures, TBBPA generally inhibited P4, 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.
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