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 beta- to alpha-myosin heavy chain (beta- and alpha-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.