Endocrine Abstracts

Thyroid hormones play an essential role for the embryonal development of the cardiovascular system including its central control mechanisms. Particularly the latter critically depends on maternal thyroid hormone, as the embryo doesn’t produce own thyroid hormone until late in pregnancy. However, the precise window of action has remained undetermined, and it is therefore unclear whether alterations in maternal thyroid hormone directly affect the offspring’s cardiac function. To address this question, we used mice heterozygous for a mutant thyroid hormone receptor α1 (TRα1), which exhibit resistance to thyroid hormone in tissues relying on TRα1 such as the heart. This was combined with maternal thyroid hormone treatments, which reactivated the mutant receptor for defined periods of time, either in the first or the second half of pregnancy. Phenotyping the offspring animals, we observed a significant increase in heart weight of male and female wildtype mice born by mothers that received thyroid hormone during the first or second half of pregnancy. Interestingly, TRα1 mutants were protected from this effect suggesting an important role of the receptor for embryonal heart development. Most remarkably, we also found a significant increase in heart rate in male mice that were exposed to elevated maternal thyroid hormone in the second half of the pregnancy independently of their own genotype, while female mice were not affected. Taken together our findings demonstrate that maternal thyroid hormone is of particular relevance during the second half of pregnancy for establishing cardiac properties, with specific effects depending on TRα1 or gender. The data therefore advocate routine monitoring of thyroid hormone levels during pregnancy to avoid adverse cardiac effects in the offspring.