Endocrine Abstracts

Environmental pollution is a major concern in households and ecosystems, many of which interfere with the homeostatic balance of living systems. Endocrine disruptors affect many biological pathways including thyroid axis. The identification of Thyroid Disruptor Chemicals and of their effects on organisms is a challenge for both regulators and industry. As thyroid signaling is highly conserved in vertebrates, zebrafish and amphibian embryos are alternative models for studying both physiological regulations and disruption. We designed a transcriptomic analysis where embryos of both species are exposed to reference compounds alone or in combination with thyroid hormones (T₃ and T₄) following the Fish Embryo Test (OECD guideline, No.236) or the Xenopus Eleutheroembryonic Thyroid Assay (OECD guideline, No.248). We selected four reference compounds: Iopanoic acid, Sodium Perchlorate, Tetrabromobisphenol A and Propylthiouracil based on their different modes of action on the thyroid signaling pathway. We analyzed their transcriptomes by RNA sequencing together with ad hoc bioinformatic pipelines. Lists of differentially regulated genes are classified in several clusters, each corresponding to a type of biological response. Despite a great diversity of biological responses, differentially regulated genes can be further classified into three categories: solely chemical dependent, solely Thyroid Hormone dependent and crosstalk responses. We first found major effects with chemicals alone, but virtually no effect with THs alone in zebrafish and the opposite in Xenopus. Second, co-treatments revealed for both species potential thyroid signaling disruption. The crosstalk responses represented a significant number of patterns in all conditions. The biological processes affected are related to metabolism (mainly related to lipid and carboxylic acid metabolism) in zebrafish and cell proliferation (covering cell cycle, DNA repair and cell division processes) in Xenopus. Stratification of the datasets with system biology uncovered additional processes affected linked to nervous and immune systems. Finally, we provide a list of candidate thyroid signaling disruption markers. In conclusion, our data provide a set of genes that represent a potential list of biomarkers of thyroid signaling disruption, and the associated effects.