2. Academic Validation
  3. Bisphenol C induces developmental defects in liver and intestine through mTOR signaling in zebrafish (Danio rerio)

Bisphenol C induces developmental defects in liver and intestine through mTOR signaling in zebrafish (Danio rerio)

  • Chemosphere. 2023 Feb 21;322:138195. doi: 10.1016/j.chemosphere.2023.138195.
Jinfeng Liu 1,  Jiebo Lin 1,  Jiafeng Chen 1,  Yasen Maimaitiyiming 2,  Kunhui Su 1,  Siqi Sun 1,  Guankai Zhan 1,  Chih-Hung Hsu 3
Affiliations

Affiliations

  • 1 Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.
  • 2 Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China; Department of Hematology of First Affiliated Hospital, and Department of Public Health, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China.
  • 3 Women's Hospital, Institute of Genetics, and Department of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China. Electronic address: ch_hsu@zju.edu.cn.
PMID: 36822516 DOI: 10.1016/j.chemosphere.2023.138195
Abstract

Bisphenol A (BPA) was widely used in the plastic products and banned in infant food containers in many countries due to the environmental and biological toxicity. As a common substitute of BPA to manufacture products, Bisphenol C (BPC) is frequently detected in human samples like infants and toddlers' urine, indicating infants and young children are at risk of BPC exposure. However, the understanding of effects of BPC exposure on early development is limited. Herein, we evaluated the early developmental toxicity of BPC and studied the underlying mechanism in a zebrafish model. We found BPC exposure leading to liver and intestinal developmental defects in zebrafish, which occurred via disruption of GPER-AKT-mTOR-RPS6 pathway. Specifically, BPC downregulated phosphorylated and total levels of mTOR, which synergistically reduced the phosphorylation of RPS6, suppressing the translation of genes essential for cell proliferation in liver and intestine such as yap1 and tcf4. Collectively, our results not only observed clear toxicity of BPC during liver and intestinal development but also demonstrated the underlying mechanism of BPC-mediated defects via disrupting the GPER-AKT-mTOR-RPS6 pathway.

Keywords

Bisphenol C; Cell proliferation; Developmental toxicity; Zebrafish; mTOR; p-RPS6.

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