Neurodevelopmental Toxicity of Bisphenol S towards Mouse Embryo and Postnatal Mouse

Abstract

To counter the ban of BPA use in food containers, manufacturers often resorted to BPA alternatives, such as BPS, to create “BPA-free” products. BPS is deemed to be safer compared to BPA given its higher light and thermal stability properties. However, although the evidence is still scarce, prenatal BPS exposure has been linked to several neurodevelopmental problems, including hyperactive behavior and impaired psychomotor development. To further clarify the issue, this study aimed to investigate the effect of maternal BPS exposure on the neurodevelopment of E16.5 embryos and P1 pups. BPS was administered orally at a dose of 500 μg/kg BW daily, while corn oil was used as the control. The brains were isolated at the designated time points and subsequently subjected to hematoxylin & eosin staining for cerebral cortex and cortical layers thickness measurement and qRT-PCR analysis of THR𝛼 which gene is highly involved in neurogenesis and brain development. The histological analysis demonstrated structural impairments of the cerebral cortex at both E16.5 and P1 time points, where there was a decrease in the overall cortical layer thickness in the BPS group compared to the control. Thickening of the neurogenesis zone (ventricular and subventricular zone) and thinning of the outer layers were also observed in the BPS group, suggesting the likelihood of BPS in inhibiting proper neuronal migration. On the other hand, no significant differences in THR⍺ expression were observed in both E16.5 and P1 time points. This result suggests that BPS may act at an earlier stage of neurodevelopment, particularly before fetal thyroid hormone maturation at E16.5.