title: Prenatal exposure to thyroid hormone is necessary for normal postnatal development of murine heart and lungs.
abstract: 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.
authors.affiliation: Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Minke
authors.initials: M
authors.lastname: van Tuyl
authors.forename: Pietjan E
authors.initials: PE
authors.lastname: Blommaart
authors.forename: Piet A J
authors.initials: PA
authors.lastname: de Boer
authors.forename: Susan E
authors.initials: SE
authors.lastname: Wert
authors.forename: Jan M
authors.initials: JM
authors.lastname: Ruijter
authors.forename: Saleem
authors.initials: S
authors.lastname: Islam
authors.forename: Jay
authors.initials: J
authors.lastname: Schnitzer
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Ellison
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Antoon F M
authors.initials: AF
authors.lastname: Moorman
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics; D000252:Calcium-Transporting ATPases; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000254:growth & development*; D007037:Hypothyroidism / Q000378:metabolism; D008168:Lung / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D012016:Reference Values; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013954:Thyroglobulin / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology / Q000502:physiology*; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; D024501:Nonmuscle Myosin Type IIB; D037662:Pulmonary Surfactant-Associated Protein A; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013954:Thyroglobulin; D013963:Thyroid Hormones; D000099211:Phospholamban; C103815:nonmuscle myosin type IIB heavy chain