A Novel Multicellular Placental Barrier Model to Investigate the Effect of Maternal Aflatoxin B1 Exposure on Fetal-Side Neural Stem Cells

Zhiwei Zhou; Dongmei Luo; Mengxue Li; Guangjie Lao; Zhiqiang Zhou; András Dinnyés; Wenming Xu; Qun Sun

doi:10.3390/toxins15050312

A Novel Multicellular Placental Barrier Model to Investigate the Effect of Maternal Aflatoxin B₁ Exposure on Fetal-Side Neural Stem Cells

Toxins (Basel). 2023 Apr 27;15(5):312. doi: 10.3390/toxins15050312.

Authors

Zhiwei Zhou¹, Dongmei Luo¹, Mengxue Li¹, Guangjie Lao¹, Zhiqiang Zhou², András Dinnyés^{1

3

4}, Wenming Xu^{5

6}, Qun Sun¹

Affiliations

¹ Key Laboratory of Bio-Resources and Eco-Environment Ministry of the Education, College of Life Sciences, Sichuan University, Chengdu 610064, China.
² Department of Food Engineering, Sichuan University, Chengdu 610064, China.
³ BioTalentum Ltd., Aulich Lajos Str. 26, 2100 Godollo, Hungary.
⁴ Department of Cell Biology and Molecular Medicine, University of Szeged, 6720 Szeged, Hungary.
⁵ Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610064, China.
⁶ Reproductive Endocrinology and Regulation Laboratory West China Second University Hospital, Sichuan University, Chengdu 610064, China.

Abstract

Ingestion of food toxins such as aflatoxin B₁ (AFB₁) during pregnancy may impair fetal neurodevelopment. However, animal model results may not be accurate due to the species' differences, and testing on humans is ethically impermissible. Here, we developed an in vitro human maternal-fetal multicellular model composed of a human hepatic compartment, a bilayer placental barrier, and a human fetal central nervous system compartment using neural stem cells (NSCs) to investigate the effect of AFB₁ on fetal-side NSCs. AFB₁ passed through the HepG2 hepatocellular carcinoma cells to mimic the maternal metabolic effects. Importantly, even at the limited concentration (0.0641 ± 0.0046 μM) of AFB_1, close to the national safety level standard of China (GB-2761-2011), the mixture of AFB₁ crossing the placental barrier induced NSC apoptosis. The level of reactive oxygen species in NSCs was significantly elevated and the cell membrane was damaged, causing the release of intracellular lactate dehydrogenase (p < 0.05). The comet experiment and γ-H2AX immunofluorescence assay showed that AFB₁ caused significant DNA damage to NSCs (p < 0.05). This study provided a new model for the toxicological evaluation of the effect of food mycotoxin exposure during pregnancy on fetal neurodevelopment.

Keywords: DNA damage; multicellular in vitro model; neural stem cells; placental barrier.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aflatoxin B1* / metabolism
Aflatoxin B1* / toxicity
Animals
DNA Damage
Female
Humans
Liver / metabolism
Mycotoxins* / metabolism
Placenta / metabolism
Pregnancy

Substances

Aflatoxin B1
Mycotoxins

Grants and funding

This study was funded by the National Key Research and Development Projects (2019YFE0103800), International Research and Development Program of Sichuan (2021YFH0060), Regional Cooperation Project (Sichuan-Guangdong) of Sichuan Science and Technology Programmes (2022YFQ0100) and Chinese-Hungarian Bilateral Project (2018-2.1.14-TÉT-CN-2018-00011, Chinese No. 8-4), Sichuan University-Luzhou oint Project of Science and Technology (2020CDLZ-17). A.D. received support from the Hungarian projects No. TKP2021-EGA-28 and 2020-1.1.5-GYORSÍTÓSÁV, financed from the National Research, Development and Innovation Fund, Hungary.