Carbamazepine disrupts molting hormone signaling and inhibits molting and growth of Eriocheir sinensis at environmentally relevant concentrations.

Highlights • Acute exposure to 1 and 10 μg/L CBZ inhibited epidermal chitobiase activity. • 10 μg/L CBZ decreased 20-HE concentration in crabs after acute exposure. • Genes related to molting hormone signaling were affected by CBZ. • Molting and growth of E. sinensis were inhibited by CBZ after chronic exposure. Abstract Carbamazepine (CBZ), one of the most frequently detected pharmaceutical compounds in aquatic environments, has recently been shown to cause chronic toxicity and endocrine disruption in a variety of non-target aquatic organisms. However, neither the effects nor the specific mechanism of CBZ action on the molting of crustaceans is well understood. The aim of this study was to investigate the effects of CBZ on the molting and growth of the Chinese mitten crab Eriocheir sinensis , a native and economically important species in China, and to elucidate the specific mechanisms through which molt inhibition occurs. Juvenile E. sinensis were treated with four nominal environmentally relevant concentrations (0.01, 0.1, 1, or 10 μg/L) of CBZ for acute (4 days) and chronic (40 days) exposures. After acute exposure, chitinase activity in the epidermis and 20-hydroxyecdysone (20-HE) concentration in the hemolymph were significantly decreased (p < 0.05) following treatment with 10 μg/L CBZ, whereas epidermal chitobiase activity significantly decreased (p < 0.05) in response to both 1 and 10 μg/L CBZ treatments. Transcript levels of the genes encoding crustacean hyperglycemic hormone (chh) and molt-inhibiting hormone (mih) in the eyestalks were also markedly induced after 1 or 10 μg/L CBZ treatment (p < 0.05), whereas the expression of genes encoding ecdysone receptor (ecr) and crustacean retinoid X receptor (rxr) in the hepatopancreas were significantly suppressed (p < 0.05) after acute exposure. Moreover, under chronic exposure, CBZ inhibited the molting and growth of E. sinensis , resulting in a longer time before molting was completed (TBM), as well as a lower molting increment (MI) with 1 or 10 μg/L treatment (p < 0.05). Collectively, these data indicate that CBZ can inhibit the molting process of E. sinensis by interfering with the activity of chitinolytic enzymes and molting hormone signaling, suggestive that carbamazepine may have long-term effects on crab development. We also confirmed that CBZ may function as an endocrine disruptor in decapod crustaceans, a phenomenon that has previously been reported in vertebrates. [ABSTRACT FROM AUTHOR]