Neurotoxicity of dibutyl phthalate in zebrafish larvae: Decreased energy acquisition by neurons.

This work was designed to investigate the neurotoxic effects of the typical plasticizer dibutyl phthalate (DBP) using zebrafish larvae as a model. The results of exhibited that zebrafish larvae exposed to DBP at concentrations of 5 µg/L and 10 µg/L exhibited brain malformations (24 h) and behavioral abnormalities (72 h). After 72 h of exposure to DBP, microglia in the brain were over-activated, reactive oxygen species (ROS) formation was increased, and apoptosis was observed. Meanwhile, it was found that neurons exhibited impaired mitochondrial structure, absent mitochondrial membrane potential and up-regulated autophagy. Further comprehensive biochemical analyses and RNA-Seq, validated by RT-qPCR, glutamate metabolism and PPAR signaling pathway were significantly enriched in the DBP stress group, this may be the main reason for the disruption of glycolysis/gluconeogenesis processes and the reduction of energy substrates for the astrocyte-neuron lactate shuttle (ANLS). In addition, the DBP-exposed group showed aberrant activation of endoplasmic reticulum (ER) stress signaling pathway, which may be related to ROS as well as neuronal apoptosis and autophagy. In conclusion, DBP-induced neurotoxicity may be the combined result of insufficient neuronal energy acquisition, damage to mitochondrial structure, apoptosis and autophagy. These results provide a theoretical basis for understanding the neurotoxic effects of DBP.

Phthalates (PAEs) and reproductive toxicity: Hypothalamic-pituitary-gonadal (HPG) axis aspects.

Phthalates (PAEs) are widely used for their excellent ability to improve plastic products. As an essential endocrine axis that regulates the reproductive system, whether dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis is involved in reproductive toxicity mediated by environmental endocrine disruptors PAEs has become a hot topic of widespread concern. This study systematically reviewed the adverse effects of multiple PAEs on the HPG axis in different models and objectively discussed the possible underlying mechanisms. The abnormal release of gonadotropin-releasing hormone and gonadotropin, dysfunction of sex hormone receptors and steroid hormone synthesis, and general damage, including cell proliferation, oxidative stress, apoptosis, and autophagy have been confirmed to be involved in this process. Although it is widely established that PAEs induce HPG axis dysfunction, the specific mechanisms involved remain unclear. From a systematic review of relevant publications, it appears that the abnormal expression of peroxisome proliferator-activated, aryl hydrocarbon, and insulin receptors mediated by PAEs is key upstream event that induces these adverse outcomes; however, this inference needs to be further verified. Overall, this study aimed to provide reliable potential biomarkers for future environmental risk assessment and epidemiological investigation of PAEs.