Multiscale Approach to Deciphering the Molecular Mechanisms Involved in the Direct and Intergenerational Effect of Ibuprofen on Mosquito Aedes aegypti

The anti-inflammatory ibuprofen is a ubiquitous surface water contaminant. However, the chronic impact of this pharmaceutical on aquatic invertebrate populations remains poorly understood. In model insect Aedes aegypti, we investigated the intergenerational consequences of parental chronic exposure to an environmentally relevant concentration of ibuprofen. While exposed individuals did not show any phenotypic changes, their progeny showed accelerated development and an increased tolerance to starvation. In order to understand the mechanistic processes underpinning the direct and intergenerational impacts of ibuprofen, we combined transcriptomic, metabolomics, and hormone kinetics studies at several life stages in exposed individuals and their progeny. This integrative approach revealed moderate transcriptional changes in exposed larvae consistent with the pharmacological mode of action of ibuprofen. Parental exposure led to lower levels of several polar metabolites in progeny eggs and to major transcriptional changes in the following larval stage. These transcriptional changes, most likely driven by changes in the expression of numerous transcription factors and epigenetic regulators, led to ecdysone signaling and stress response potentiation. Overall, the present study illustrates the complexity of the molecular basis of the intergenerational pollutant response in insects and the importance of considering the entire life cycle of exposed organisms and of their progeny in order to fully understand the mode of action of pollutants and their impact on ecosystems.