Neurodevelopmental toxicity and mechanism of action of monoethylhexyl phthalate (MEHP) in the developing zebrafish (Danio rerio)

Abstract

Monoethylhexyl phthalate (MEHP) is the primary metabolite of di(2-ethylhexyl) phthalate (DEHP), the most prevalent phthalate plasticiser globally. It has been demonstrated that MEHP exerts more potent toxic effects than DEHP. Nevertheless, the full extent of the toxicity of MEHP to neurodevelopmental organisms remains unclear. Accordingly, the present study was designed to investigate the neurodevelopmental toxicity of MEHP exposure and the underlying molecular mechanisms. Zebrafish juveniles were exposed to different concentrations of MEHP (7.42, 14.84, 29.68 and 74.2 μg/L) for a period of four weeks. Immunohistological evidence indicated that MEHP exposure resulted in oxidative stress and apoptosis in the developing zebrafish brain. Subsequently, the neurobehaviour of zebrafish larvae was evaluated, and it was determined that MEHP significantly disrupted their locomotor capacity, motor vigor, and social conduct. Furthermore, HE staining revealed damage to brain neurons, which may be linked to impaired synthesis and conduction of inter-synaptic neurotransmitters. Transcriptomic analyses indicated that MEHP may affect the expression levels of genes in the P53 signalling pathway and signalling pathways related to the development of the nervous system. This results in impaired functions, including nerve conduction and neuronal development. Additionally, it induces oxidative stress, which leads to significant brain cell apoptosis and, ultimately, neurotoxicity in developing zebrafish.