Microplastics exposure affects neural development of human pluripotent stem cell-derived cortical spheroids

Abstract

Plastics have been part of our ecosystem for about a century and their degradation by different environmental factors produce secondary microplastics (MPs). To date, the impact of MPs on human health has not been well investigated. To understand the possible effects of polystyrene-MPs (PS-MPs) on the human brain, a 3D model of human forebrain cortical spheroids has been derived, which mimics early development of human cerebral cortex. The spheroids were exposed to 100, 50, and 5 µg/mL of 1 µm and 10 µm PS-MPs during day 4–10 and day 4–30. The short-term MP exposure showed the promoted proliferation and high gene expression of Nestin, PAX6, ATF4, HOXB4 and SOD2. For long-term exposure, reduced cell viability was observed. Moreover, changes in size and concentration of PS-MPs altered the gene expression of DNA damage and neural tissue patterning. In particular, β-tubulin III, Nestin, and TBR1/TBR2 gene expression decreased in PS-MP treated conditions compare to the untreated control. The results of this study suggest that the size- and concentration-dependent exposure to PS-MPs can adversely affect embryonic brain-like tissue development in forebrain cerebral spheroids. This study has significance in assessing environmental factors in neurotoxicity and degeneration in human.