Mixtures of Aluminum and Indium Induce More than Additive Phenotypic and Toxicogenomic Responses in <i>Daphnia magna</i>

Aquatic
systems are contaminated by many metals but their effects
as mixtures on organisms are not well understood. Here, we assessed
effects of aluminum with fairly well-known modes of actions and indium,
an understudied emerging contaminant from electronics, followed by
studying equi-effective mixtures thereof. We report acute and adverse
phenotypic effects in Daphnia magna adults and global
transcriptomic effects employing RNA sequencing in neonates. The mixture
induced more than additive activity in mortality and in physiological
effects, including growth and reproduction. Similarly, transcriptomic
effects were more than additive, as indicated by a markedly higher
number of 463 differentially expressed transcripts in the mixture
and by distinct classes of genes assigned to several biological functions,
including metabolic processes, suggesting depleted energy reserves,
which may be responsible for the observed impaired reproduction and
growth. A gene set enrichment analysis (GSEA) of a priori known response
pathways for aluminum confirmed activation of distinct molecular pathways
by indium. Our study is highlighting more than additive effects at
the transcriptional and physiological level and is providing a state-of-the
art approach to mixture analysis, which is important for risk assessment
of these metals and metal mixtures.