Maternal thyroid hormone programs cardiovascular functions in the offspring

Background: Maternal thyroid hormone (TH) plays an essential role for fetal development, especially for the cardiovascular system and its central control. However, the precise consequences of altered TH action during the different periods in pregnancy remain poorly understood. Methods: To address this question, we used mice heterozygous for a mutant thyroid hormone receptor a1 (TRa1) and wild-type controls that were born to wild-type mothers treated with 3,3¢,5-triiodothyronine (T3) during the first or the second half of pregnancy. We then phenotyped the offspring animals as adults by in vivo measurements and postmortem tissue analyses. Results: Maternal T3 treatment in either half of the pregnancy did not affect postnatal growth development. Serum thyroxine and hypophyseal thyrotropin subunit beta or deiodinase type II expression was also not affected in any group, only TRa1 mutant males exhibited a reduction in serum T3 levels after the treatment. Likewise, hepatic deiodinase type I was not altered, but serum selenium levels were reduced by the maternal treatment in wild-type offspring of both genders. Most interestingly, a significant increase in heart weight was found in adult wild-types born to mothers that received T3 during the first or second half of pregnancy, while TRa1 mutant males were protected from this effect. Moreover, we detected a significant increase in heart rate selectively in male mice that were exposed to elevated maternal T3 in the second half of the pregnancy. Conclusion: Taken together, our findings demonstrate that maternal TH is of particular relevance during the second half of pregnancy for establishing cardiac properties, with specific effects depending on TRa1 or gender. The data advocate routinely monitoring TH levels during pregnancy to avoid adverse cardiac effects in the offspring.