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

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 develop-mental 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.

Automated summary

Bisphenol C (BPC), a common substitute for Bisphenol A (BPA), was found to cause liver and intestinal developmental defects in zebrafish by disrupting the GPER-AKT-mTOR-RPS6 pathway. These results not only revealed the toxicity of BPC during organ development, but also provided insights into the underlying mechanism.