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- Molecular and cellular mechanisms of ioxynil and diethylstilestrol disruption of cardiac and thyrocyte development and homeostasisPublication . Li, Yifeng; Power, Deborah M.Endocrine disrupting chemicals (EDCs) are compounds that interfere with endocrine systems, induce alterations in their functionality, and give rise to numerous adverse effects that have been documented in animals and ecosystems. The herbicide ioxynil (IOX) and the synthetic estrogen diethylstilbestrol (DES) are two chemicals still in use, which are environmentally relevant contaminants that act as EDCs. In humans, prenatal exposure to DES is associated with an increased incidence and prevalence of cardiac defects. IOX may disrupt the thyroid system by binding to transthyretin (TTR) and provoke thyroid tumors in rats. The main objective of this thesis was to determine how IOX and DES disrupt the crosstalk between the developing thyroid gland and cardiovascular system in zebrafish. An invertebrate bioindicator species, Mytilus coruscus, was included in the study to comprehend the effects of IOX and DES on a bivalve and contribute to a broader understanding of endocrine disruption in both invertebrate and vertebrate organisms. The core achievements were a) characterization of heart function and cardiovascular and thyroid development in IOX- and DES-exposed zebrafish embryos. Transcriptome analysis of vascular endothelial cells of zebrafish embryos that elucidated compound-specific molecular effects associated with endothelial functions; b) identification of the effects of IOX and DES on the physiology of the heart and thyroid in juvenile zebrafish; c) characterization of the effects of IOX and DES on cardiac performance and shell growth of juvenile M. coruscus. Transcriptome analysis of juveniles revealed genes related to cardiac function, neuroendocrine regulation, and detoxification were affected. The findings revealed that IOX and DES exposure had a disruptive effect at a molecular and functional level on the cardiovascular system of a vertebrate (zebrafish) and an invertebrate (M. coruscus), suggesting that these chemicals function as cardiovascular disruptors in both phyla. Overall, the study highlights for the first time the potential at both a molecular and functional level of adverse outcomes for both fish and bivalves of exposure to IOX and DES in the environment, suggesting they are EDCs with broad impacts across multiple organisms.