Environmentally relevant exposure to TBBPA and its analogues may not drastically affect human early cardiac development. (1st August 2022)

• Record Type: Journal Article
• Authors: Zhao, Miaomiao; Yin, Nuoya; Yang, Renjun; Li, Shichang; Zhang, Shuxian; Faiola, Francesco
• Is Part Of: Environmental pollution. Volume 306(2022)
• Publication Date: 2022-08-01
• Subjects: Halogenated flame retardants (HFRs) -- Human embryonic stem cells (hESCs) -- Embryoid bodies (EBs) -- Cardiomyocyte differentiation -- Developmental toxicity; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.119467
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Tetrabromobisphenol A (TBBPA) and its substitutes and derivatives have been widely used as halogenated flame retardants (HFRs), in the past few decades. As a consequence, these compounds are frequently detected in the environment, as well as human bodily fluids, especially umbilical cord blood and breast milk. This has raised awareness of their potential risks to fetuses and infants. In this study, we employed human embryonic stem cell differentiation models to assess the potential developmental toxicity of six TBBPA-like compounds, at human relevant nanomolar concentrations. To mimic early embryonic development, we utilized embryoid body-based 3D differentiation in presence of the six HFRs. Transcriptomics data showed that HFR exposure over 16 days of differentiation only interfered with the expression of a few genes, indicating those six HFRs may not have specific tissue/organ targets during embryonic development. Nevertheless, further analyses revealed that some cardiac-related genes were dysregulated. Since the heart is also the first organ to develop, we employed a cardiac differentiation model to analyze the six HFRs' potential developmental toxicity in more depth. Overall, HFRs of interest did not significantly disturb the canonical WNT pathway, which is an essential signal transduction pathway for cardiac development. In addition, the six HFRs showed only mild changes in gene expression levels for cardiomyocyte markers, such as NKX2.5, MYH7, and MYL4, as well as a significant down-regulation of some but not all the epicardial and smooth muscle cell markers selected. Taken together, our results show that the six studied HFRs, at human relevant concentrations, may impose negligible effects on embryogenesis and heart development. Nevertheless, higher exposure doses might affect the early stages of heart development. Graphical abstract: Image 1 Highlights: Six TBBPA-like compounds' potential toxic effects were assessed with hESCs. The six chemicals' low doses dysregulated a few genes during EB differentiation. TBBPA-like compounds mildly affected some hESC cardiac differentiation genes. TBBPA-BHEE was the most cytotoxic among the six TBBPA-like chemicals.