Endocrine Abstracts

Lifelong thyroid health depends on establishment of thyroid gland structure and function during early life development. However, thyroid development can be disrupted and lead to early- or adult life thyroid disorders. Still, the molecular machinery underpinning thyroid gland development remains poorly understood, particularly after the onset of fetal thyroid function. Here we used bulk-RNA-barcoding and sequencing (BRB-seq) to map the thyroid gland transcriptome as it undergoes transcriptional reprogramming after the onset of fetal thyroid gland function. We found 1619 differentially expressed genes (DEGs) during rat thyroid gland development from gestation day 21 to postnatal days 3, 6, 16 and 22. The DEGs partitioned into 6 clusters that display distinct temporal transcriptional patterns. Highly expressed genes in fetuses and neonates were primarily related to cell division, development and morphogenesis. This immaturity of the thyroid gland, even after the onset of thyroid function, was verified histologically, as the fetal thyroids displayed a dense structure with very little follicular lumen. Later on in postnatal development, as thyroid hormone concentrations peak, thyroid gland structure was more mature with larger follicles. This was also reflected in the postnatal transcriptome where genes important for thyroid hormone synthesis, such as Tpo, Slc5a5(NIS) and Nkx2-1, were upregulated. In addition to the temporal DEGs, we identified 205 DEGs between males and females. Some of these DEGs were related to thyroid hormone synthesis, Tg, Duox1 and Duox2, but the enriched terms also showed that developmental processes as well as the immune system and response to hormones was different between males and females. Thus, it is possible that these differences mediate a sex-specific susceptibility to external stressors such as environmental chemicals. Our results show that, even after the onset of thyroid function, the thyroid gland is still developing with a distinct and sexually dimorphic transcriptional landscape. Disruptions to this transcriptional reprogramming could alter development and thus susceptibility to thyroid disorders in adult life.