2. Academic Validation
  3. TBBPA, TBBPS, and TCBPA disrupt hESC hepatic differentiation and promote the proliferation of differentiated cells partly via up-regulation of the FGF10 signaling pathway

TBBPA, TBBPS, and TCBPA disrupt hESC hepatic differentiation and promote the proliferation of differentiated cells partly via up-regulation of the FGF10 signaling pathway

  • J Hazard Mater. 2021 Jan 5;401:123341. doi: 10.1016/j.jhazmat.2020.123341.
Renjun Yang 1,  Shuyu Liu 2,  Xiaoxing Liang 1,  Nuoya Yin 1,  Linshu Jiang 3,  Yang Zhang 4,  Francesco Faiola 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China; Wellcome Trust/CRUK Gurdon Institute, Department of Pathology, University of Cambridge, Cambridge, CB2 1QN, UK.
  • 3 Beijing Key Laboratory for Dairy Cow Nutrition, Beijing University of Agriculture, Beijing, 102206, China.
  • 4 Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China. Electronic address: david19872005@163.com.
  • 5 State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: faiola@rcees.ac.cn.
PMID: 32653787 DOI: 10.1016/j.jhazmat.2020.123341
Abstract

Halogenated flame retardants (HFRs), including Tetrabromobisphenol A (TBBPA), Tetrabromobisphenol S (TBBPS), and Tetrachlorobisphenol A (TCBPA), are widely applied in the manufacturing industry to improve fire safety and can be detected in pregnant women's serum at nanomolar levels. Thus, it is necessary to pay attention to the three HFR potential development toxicity, which has not been conclusively addressed yet. The liver is the main organ that detoxifies our body; TBBPA exposure may lead to increased liver weight in rodents. Therefore, in this study, we assessed the developmental hepatic toxicity of the three HFRs with a human embryonic stem cell hepatic differentiation-based system and transcriptomics analyses. We mostly evaluated lineage fate alterations and demonstrated the three HFRs may have common disruptive effects on hepatic differentiation, with TCBPA being significantly more potent. More specifically, the three HFRs up-regulated genes related to cell cycle and FGF10 signaling, at late stages of the hepatic differentiation. This indicates the three chemicals promoted hepatoblast proliferation likely via up-regulating the FGF10 cascade. At the same time, we also presented a powerful way to combine in vitro differentiation and in silico transcriptomic analyses, to efficiently evaluate hazardous materials' adverse effects on lineage fate decisions during early development.

Keywords

Developmental hepatic toxicity; FGF10; Halogenated flame retardants; Hepatic differentiation; Transcriptomics analysis.

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