Acrylamide exposure represses neuronal differentiation, induces cell apoptosis and promotes tau hyperphosphorylation in hESC-derived 3D cerebral organoids

Food Chem Toxicol. 2020 Oct:144:111643. doi: 10.1016/j.fct.2020.111643. Epub 2020 Aug 5.


Acrylamide (ACR) is a common food contaminant with neurotoxic effects that are formed in the Maillard browning reaction during the heat processing of food. Importantly, pregnant women are also exposed to ACR in food during pregnancy and thus, the fetus is likely affected. However, the mechanisms of ACR-caused neurotoxicity on human brain development are still unclear. Many recent studies employed cerebral organoids based on human embryonic stem cells (hESC) for investigating human neurodevelopmental disorders and toxicity. Here, we generated hESC-derived cerebral organoids to evaluate the neurodevelopmental toxicity of ACR. The results indicated that exposure to ACR significantly altered the transcriptional profile, increased nuclear factor erythroid 2-related factor 2 (NRF2)-mediated gene expression, induced cell apoptosis, repressed neuronal differentiation, and promoted tau hyperphosphorylation in cerebral organoids, which may contribute to ACR-induced neurodevelopmental toxicity. These results indicate that the risk of transplacental exposure of the fetus to ACR should be evaluated and pregnant mothers should limit their exposure to ACR.

Keywords: Acrylamide; Apoptosis; Cerebral organoid; Neuronal differentiation; p-tau.

MeSH terms

  • Acrylamide / toxicity*
  • Apoptosis / drug effects*
  • Cell Differentiation / drug effects*
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • Neurons / cytology
  • Neurons / drug effects*
  • Organoids / metabolism*
  • Phosphorylation
  • tau Proteins / metabolism*


  • MAPT protein, human
  • tau Proteins
  • Acrylamide