title: Prenatal iodine deficiency results in structurally and functionally immature lungs in neonatal rats.
abstract: Maternal hypothyroidism affects postnatal lung structure. High prevalence of hypothyroxinemia (low T4, normal T3) in iodine-deficient pregnant women and associated risk for neuropsychological development along with high infant/neonatal mortality ascribed to respiratory distress prompted us to study the effects of maternal hypothyroxinemia on postnatal lung development. Female Sprague Dawley rats were given a low-iodine diet (LID) with 1% KClO(4) in drinking water for 10 days, to minimize thyroid hormone differences. Half of these rats were continued on iodine-deficient diet; ID (LID with 0.005% KClO(4)) for 3 mo, whereas the rest were switched to an iodine-sufficient diet; IS [LID + potassium iodide (10 μg iodine/20 g of diet + normal drinking water)]. Pups born to ID mothers were compared with age-matched pups from IS mothers at postnatal days 8 (P8) and 16 (P16) (n = 6-8/group). ID pups had normal circulating T3 but significantly low T4 levels (P < 0.05) and concomitantly approximately sixfold higher thyroid hormone receptor-β mRNA in alveolar epithelium. Lung histology revealed larger and irregularly shaped alveoli in ID pups relative to controls. Lung function was assessed at P16 using a double-chambered plethysmograph and observed reduced tidal volume, peak inspiratory and expiratory flow, and dynamic lung compliance in ID pups compared with IS pups. Significant lowering of surfactant protein (SP)-B and SP-C mRNA and protein found in ID pups at P16. ID pups had 16-fold lower matrix metalloproteinase-9 mRNA levels in their alveolar epithelium. In addition, mRNA levels of thyroid transcription factor-1 and SP-D were significantly higher (3-fold) compared with IS pups. At P16, significantly lower levels of SP-B and SP-C found in ID pups may be responsible for immature lung development and reduced lung compliance. Our data suggest that maternal hypothyroxinemia may result in the development of immature lungs that, through respiratory distress, could contribute to the observed high infant mortality in ID neonates.
authors.affiliation: Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India. madangodbole@yahoo.co.in.
authors.forename: Madan M
authors.initials: MM
authors.lastname: Godbole
authors.forename: Geeta
authors.initials: G
authors.lastname: Rao
authors.forename: B N
authors.initials: BN
authors.lastname: Paul
authors.forename: Vishwa
authors.initials: V
authors.lastname: Mohan
authors.forename: Preeti
authors.initials: P
authors.lastname: Singh
authors.forename: Drirh
authors.initials: D
authors.lastname: Khare
authors.forename: Satish
authors.initials: S
authors.lastname: Babu
authors.forename: Alok
authors.initials: A
authors.lastname: Nath
authors.forename: P K
authors.initials: PK
authors.lastname: Singh
authors.forename: Swasti
authors.initials: S
authors.lastname: Tiwari
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007223:Infant; D007455:Iodine / Q000172:deficiency*; D008168:Lung / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D008170:Lung Compliance; D009687:Nuclear Proteins / Q000096:biosynthesis; D010455:Peptides / Q000378:metabolism; D010991:Plethysmography; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology; D037042:Thyroid Hormone Receptors beta / Q000096:biosynthesis; D000074482:Thyroid Nuclear Factor 1; D013974:Thyroxine / Q000172:deficiency*; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: C000614412:NKX2-1 protein, human; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D010455:Peptides; D037701:Pulmonary Surfactant-Associated Protein B; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger; D037042:Thyroid Hormone Receptors beta; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C077063:Sftpc protein, rat; D007455:Iodine; D013974:Thyroxine