Validating a Novel Model of Induced-Thyrotoxicosis in White Leghorn Chicken

Abstract

Thyroid hormones play a critical role in growth and maintenance in all organ systems. In pregnant women, excess thyroid hormones in circulation, or thyrotoxicosis, has been associated with various fetal abnormalities including craniosynostosis (CS), the premature fusion of the cranial sutures. The mechanism of thyrotoxicosis-induced CS is elusive and therefore requires further investigation. To enhance current knowledge and uncover this indefinable mechanism, we have proposed a new model of induced-thyrotoxicosis mimicking maternal thyrotoxicosis using White Leghorn chicken embryos exposed to a low dose of 25 ng thyroxine (T₄) on developmental days 11 and 15. While our overall objective was to establish this model to study the effects of maternal thyrotoxicosis in the development of CS in utero, this model may be effective for studying other developmental conditions related to increased circulating thyroid hormones during embryonic development. Our model maintained over 90% survivability while inducing morphological and molecular changes in target tissue types, including bone. We confirmed thyrotoxicosis in the chicken embryos by quantifying levels of T₄ in serum by ELISA and observed attenuated body growth with thyroxine exposure supported by a 20% decrease in body mass (p<0.001), 5% decrease in body length (p<0.001), 20% decrease in third metatarsal length (p<0.01), and 7% decrease in tibiotarsal length (p<0.01). Our results support that our proposed model of induced-thyrotoxicosis in developing chicken embryos will be efficient for studying the effects of increased circulating thyroid hormones on the development of multiple organ systems.