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Transcriptomic responses to cytotoxic drug cisplatin in water flea Daphnia magna
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2022-08-24 , DOI: 10.1016/j.etap.2022.103964
Jingya Ren 1 , Fangshe Yang 1 , Ning Ding 1 , Jiezhang Mo 2 , Jiahua Guo 1
Affiliation  

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.



中文翻译:

水蚤 Daphnia magna 对细胞毒药物顺铂的转录组学反应

细胞毒性药物已被欧盟认定为水生环境中的潜在威胁。作为一种典型的细胞毒药物,长期暴露于环境相关浓度的顺铂对甲壳类动物健康的影响及其分子机制仍未确定。在这项研究中,最初评估了顺铂暴露引起的大型蚤的生长和繁殖。虽然 2 μg L -1、20 μg L -1和 200 μg L -1治疗组的表型没有改变,但 500 μg L -1的顺铂将每窝的后代数量显着减少至 8-13 只新生儿,低于对照组的 13-27 只新生儿。除了第一次怀孕的时间延迟外,第 7 天体长减少了大约 12.13%。同时,所有水蚤在暴露于 500 µg L -1顺铂 17 天后死亡。转录组分析生物测定进行了 10 天,以探索分子水平的变化。简而言之,980 个(257 个上调和 723 个下调)、429 个(182 个上调和 247 个下调)和 1984 个(616 个上调和 1368 个下调)基因在低水平差异表达(adj p  < 0.05) (2 μg L -1 )、中 (200 μg L -1 ) 和高 (500 μg L -1) 顺铂治疗组,分别。差异表达基因主要富集于消化吸收、神经传导、内分泌干扰和循环相关通路。具体而言,消化分泌和营养吸收以及神经元传导通路的下调可能导致参与生长和繁殖的能量供应不足,阻碍卵巢发育和细胞生长。卵巢类固醇和松弛素信号通路的下调可能与后代数量减少和妊娠延迟有关,而D. magna体长的减少可能归因于胰岛素分泌通路的富集。此外,D. magna的死亡可能是由于心肌细胞收缩和凋亡过程中基因的表达减少所致。总之,这项研究揭示了顺铂在模型水蚤中的潜在毒性机制。

更新日期:2022-08-27
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