EDCs trigger immune-neurotransmitter related gene expression, and cause histological damage in sensitive mud crab Macrophthalmus japonicus gills and hepatopancreas.

Endocrine-disrupting chemicals (EDCs), distributed at various concentrations in freshwater and marine ecosystems, affect the survival, reproduction, and behavior of wide ranges organisms. Most toxicology studies on EDCs have focused on the endocrine system of invertebrates, and research on invertebrate neurotransmitters is limited. In the present study, we investigated the expression of Macrophthalmus japonicus genes encoding γ-aminobutyric acid transporter subtype 2 (GAT-2) and glutamine synthetase (GS), which play important roles as neurotransmitters at synapses. We observed differences in the mRNA expression levels of GAT-2 and GS as well as histological changes in various tissues after exposure to bisphenol-A (BPA) and di-(2-ethylhexyl) phthalate (DEHP). The amino acid sequences of M. japonicus GAT-2 and GS formed separate branches in crustaceans, fish, insects, and mammals. M. japonicus GAT-2 and GS expression levels were highest in the gills, hepatopancreas, and stomach, and showed different between DEHP or BPA treatments. In particular, hepatopancreas GS expression on Day 1, the first step in the presynaptic process, was upregulated after BPA and DEHP exposure, while GAT-2, sequential step in the presynaptic process, was significantly elevated only in DEHP. After BPA treatments, gill GS expression was increased at all concentrations, whereas GAT-2 expression was overall down regulations. In contrast, in DEHP treatment groups hepatopancreatic GS and GAT-2 expression at Day 1 was only significantly higher and all groups including gill GS and GAT-2 expression were downregulation. Histological changes in the gills and hepatopancreas were observed in a concentration-dependent manner. Accordingly, BPA and DEHP exposure in crabs could be stimulate neurotransmitter gene expression and alter the morphological structure of gill and hepatopancreas.