Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs

Minke Van Tuyl, Pietjan E. Blommaart, Piet A.J. De Boer, Susan E. Wert, Jan M. Ruijter, Saleem Islam, Jay Schnitzer, Aaron R. Ellison, Dick Tibboel, Antoon F.M. Moorman, Wouter H. Lamers

Research output: Contribution to journalArticlepeer-review

59 Citations (Scopus)


Maternal hypothyroxinemia during early pregnancy poses an increased risk for poor neuropsychological development of the fetus. We tested the hypothesis that maternal hypothyroidism before the onset of fetal thyroid function also affects postnatal development of heart and lungs. This question was addressed in transgenic mice that express herpes simplex virus thymidine kinase in their thyroidal follicle cells. Treatment with ganciclovir rendered these mice severely hypothyroid because viral thymidine kinase converts ganciclovir into a cytotoxic nucleoside analog. Since ganciclovir crosses the placenta, it also destroyed the thyroid of transgenic embryos while leaving the thyroids of nontransgenic littermates unaffected. Hypothyroidism of both mother and fetus did not affect prenatal heart and lung development. However, the postnatal switch from β- to α-myosin heavy chain (β- and α-MHC, respectively) gene expression and the increase of SERCA-2a mRNA expression did not occur in the ventricular myocardium of either the transgenic (thyroid destroyed) or nontransgenic (intact thyroid) offspring of hypothyroid mothers. Similarly, postnatal animals of the latter two groups retained elevated surfactant protein (SP) A, B, and C mRNA levels in their alveolar epithelium. In hypothyroid pups from hypothyroid mothers, these changes were accompanied by decreased alveolar septation. Our study shows that these effects of maternal hypothyroidism become manifest after birth and are aggravated by the concomitant existence of neonatal hypothyroidism.

Original languageEnglish
Pages (from-to)104-117
Number of pages14
JournalDevelopmental Biology
Issue number1
Publication statusPublished - 1 Aug 2004
Externally publishedYes


  • ED
  • Heart development
  • Lung development
  • MHC
  • Maternal hypothyroidism
  • Myosin heavy chain
  • ND
  • OD
  • PLB
  • SP
  • Surfactant proteins
  • embryonic day
  • myosin heavy chain
  • neonatal day
  • optical density
  • phospholamban
  • sarcoplasmatic reticulum ATPase
  • surfactant protein


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