1 research outputs found
TBBPA and Its Alternatives Disturb the Early Stages of Neural Development by Interfering with the NOTCH and WNT Pathways
Tetrabromobisphenol
A (TBBPA), as well as its alternatives Tetrabromobisphenol
S (TBBPS) and Tetrachlorobisphenol A (TCBPA), are widely used halogenated
flame retardants. Their high detection rates in human breast milk
and umbilical cord serum have raised wide concerns about their adverse
effects on human fetal development. In this study, we evaluated the
cytotoxicity and neural developmental toxicity of TBBPA, TBBPS, and
TCBPA with a mouse embryonic stem cell (mESC) system, at human body
fluid and environmental relevant doses. All the three compounds showed
similar trends in their cytotoxic effects. However, while TBBPA and
TBBPS stimulated ESC neural differentiation, TCBPA significantly inhibited
neurogenesis. Mechanistically, we demonstrated that, as far as the
NOTCH (positive regulator) and WNT (negative regulator) pathways were
concerned, TBBPA only partially and slightly disturbed them, whereas
TBBPS significantly inhibited the WNT pathway, and TCBPA down-regulated
the expression of NOTCH effectors but increased the WNT signaling,
actions which both inhibited neural specification. In conclusion,
our findings suggest that TBBPS and TCBPA may not be safe alternatives
to TBBPA, and their toxicity need to be comprehensively evaluated