Transcriptomic responses to cytotoxic drug cisplatin in water flea Daphnia magna

Abstract

Cytotoxic drugs have been recognized by the European Union as the potential threat in the aquatic environment. As a typical cytotoxic drug, effects of long-term exposure to cisplatin at the environmentally relevant concentrations on the crustacean health and its molecular mechanism remain undetermined. In this study, the growth and reproduction of Daphnia magna resulting from cisplatin exposure were initially assessed. While the phenotypes were not altered in 2 μg L^-1, 20 μg L^-1, and 200 μg L^-1 treatment groups, cisplatin at 500 µg L^-1 significantly reduced the offspring number to 8-13 neonates in each brood, which was lower than 13-27 neonates in the control group. In addition to the delay in the time of first pregnancy, the body length was decreased by approximate 12.13% at day 7. Meanwhile, all daphnids died after exposure to 500 µg L^-1 cisplatin for 17 days. Transcriptome profiling bioassays were performed for 10 days to explore the alternation at the molecular level. Briefly, 980 (257 up- and 723 down-regulated), 429 (182 up- and 247 down-regulated) and 1984 (616 up-regulated and 1368 down-regulated) genes were differentially expressed (adj p < 0.05) in low (2 μg L^-1), medium (200 μg L^-1) and high (500 μg L^-1) cisplatin treatment groups, respectively. Differentially expressed genes were primarily enriched in the digestion and absorption, nerve conduction, endocrine interference, and circulatory related pathways. Specifically, the down-regulated digestive secretion and nutrient absorption and neuronal conduction pathways may lead to insufficient energy supply involved in growth and reproduction, and hinder ovarian development and cell growth. Down-regulation of ovarian steroids and relaxin signaling pathways may be related to the reduction of offspring number and delayed pregnancy, and reduced body length of D. magna may attribute to the enrichment of insulin secretion pathway. In addition, the death of D. magna may result from the reduced expression of genes in cardiomyocyte contraction and apoptosome processes. Taken together, this study revealed the potential toxic mechanism of cisplatin in a model water flea.

Keywords: Aquatic invertebrates; Endocrine and circulatory system; Energy metabolism; Next generation sequencing; Reproductive toxicity.