Effects of single and combined low concentrations of neuro-active drugs on Daphnia magna reproduction and transcriptomic responses.

Abstract

Assessing the risk of neuro-active pharmaceuticals in the environment requires an understanding of their joint effects at low concentrations across species. Here, we assessed reproductive and transcriptional effects of single and ternary equi-effective mixture exposure to propranolol, diazepam and carbamazepine on the crustacean Daphnia magna at environmentally relevant concentrations. The three compounds enhanced reproduction in adults, and induced specific transcriptome changes in pre-adolescent individuals. Comparison of the results from single exposures to a ternary equi-effective mixture of the three compounds, showed additive action. Transcriptomic analyses identified 3248 genes affected by at least one of the treatments, which were grouped into four clusters. Two clusters (1897 gene transcripts in total) behaved similarly, appearing either over- or under-represented relative to control, in all single and mixture treatments. The third and fourth clusters grouped genes differently transcribed upon exposure to diazepam and propranolol, respectively. Functional transcriptomics analysis indicated that the four clusters shared major de-regulated signalling pathways implicated on energy, growth, reproduction, and neurologically- related processes, which may be responsible for the observed reproductive effects. Thus, our study showed additive effects at the transcriptional and physiological level and is providing a novel approach to the analysis of environmental relevant mixtures of neuro-active compounds.