Triiodothyronine-induced changes in the zebrafish transcriptome during the eleutheroembryonic stage: implications for...

Thyroid disruption during early development is a current matter of concern due to its significant human health implications. We present here a transcriptome analysis of thyroid hormone-regulated genes in zebrafish during the eleutheroembryonic stage (days 2-5 post fertilization) to detect potential markers of thyroid disruption. Exposure to 3,5,3'-triiodo-l-thyroxine (T3, 50 nM) induced changes in a minor portion (less than 2%) of the zebrafish transcriptome, with a significant fraction of genes involved in the haematopoietic system, eye formation, and ossification/skeletal system, including the thyroid receptor thra gene. Some of the transcriptomic changes were reflected macroscopically, as an allometric decrease of eye size and an increase on thra hybridization signal in the skeletal tissue. Using this information, changes on transcription of three genes (adult alpha globin gene si:ch211-5 k11.6, embryonic globin gene hbae3, and long wavelength cone opsin gene opn1/w1) were analyzed to monitor the effect of the suspected thyroid disrupter bisphenol A (BPA) on the thyroid system during this period of development of zebrafish. BPA acted as a weak T3 agonist when tested alone, but it strongly enhanced the effect of subsaturating concentrations of T3. In thyroxine immunofluorescence quantitative disruption tests (TIQDT), BPA did not prevent the ability of thyroid follicles to synthesize thyroxine, a landmark for direct goitrogens. Our results suggest that BPA potentiates the effect of endogenous T3 in early development and demonstrate the requirement for the use of in vivo, multi-endpoint methods to evaluate thyroid disruption hazards on early developmental processes in vertebrates.