A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure

Aynur Abdulla; Haoni Yan; Shujin Chen; Leqi Wu; Xu-Sen Chen; Yizhi Zhang; Manlin Zhang; Tsz Yui Zhuang; Khan Zara Ahmad; Jinjin Lin; Xianting Ding; Lai Jiang

doi:10.1016/j.bios.2024.116754

A multichannel microfluidic device for revealing the neurotoxic effects of Bisphenol S on cerebral organoids under low-dose constant exposure

Biosens Bioelectron. 2024 Sep 14:267:116754. doi: 10.1016/j.bios.2024.116754. Online ahead of print.

Authors

Aynur Abdulla¹, Haoni Yan², Shujin Chen³, Leqi Wu⁴, Xu-Sen Chen⁴, Yizhi Zhang⁴, Manlin Zhang⁴, Tsz Yui Zhuang⁴, Khan Zara Ahmad⁵, Jinjin Lin⁶, Xianting Ding⁷, Lai Jiang⁸

Affiliations

¹ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200092, China; State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
² Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200092, China.
³ Ministry of Education, Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China.
⁴ State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.
⁵ Department of Laboratory Medicine, Division of Pathology, Karolinska Institute, Sweden.
⁶ State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China; School of Psychology, Shaanxi Normal University, Xi' an 710062, Shaanxi Province, China.
⁷ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200092, China; State Key Laboratory of Oncogenes and Related Genes, Institute for Personalized Medicine, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China. Electronic address: [email protected].
⁸ Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200092, China. Electronic address: [email protected].

PMID: 39332252
DOI: 10.1016/j.bios.2024.116754

Abstract

Bisphenol S is a widely used plasticizer in manufacturing daily supplies, while little was known about its adverse effect on human health, especially on fetal brain development. Due to the complexity and subtlety of the brain, it remains challenging to reveal the hazardous effects of environmental pollution on human fetal brain development. Taking advantage of stem cell application, cerebral organoids generated from stem cells are becoming powerful tools for understanding brain development and drug toxicity testing models. Here, we developed a microfluidic chip for cerebral organoid culturing to reveal the neurotoxicity of low-dose constant BPS exposure on cerebral organoids. The organoids in our microfluidic system could be continuously cultured for 34 days and expressed all the essential properties of the cerebral organoids. Exposure to BPS was initiated from day 20 for concessive two weeks. The neurotoxic effects were evaluated by immunofluorescence staining and proteomics, and verified by quantitative real-time PCR. Our results indicated BPS exposure would inhibit neuron differentiation, hinder the Wnt signaling pathway, and cause alteration of signaling molecule expressions in brain regionalization. Even exposure to a low dose of BPS constantly might cause neurotoxicity during fetal brain development. Altogether, the multichannel microfluidic chip offers a general platform technique to reveal the effects of different hazardous chemicals on cerebral organoids.

Keywords: Bisphenol S; Cerebral organoids; Microfluidic chip; Neurotoxicity.