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Published on: November 20, 2015
Prenatal iodine deficiency results in structurally and functionally immature lungs in neonatal rats
Madan M Godbole1, Geeta Rao, B N Paul
1Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, India. madangodbole@yahoo.co.in.
Insights
Maternal hypothyroxinemia, common in iodine deficiency, leads to immature lung development in pups. This may increase infant mortality due to respiratory distress.
Area of Science:
- Endocrinology
- Pulmonology
- Developmental Biology
Background:
- Maternal hypothyroxinemia (low thyroxine, normal triiodothyronine) is prevalent in iodine-deficient pregnancies.
- It is linked to adverse neurodevelopmental outcomes and increased infant mortality from respiratory distress.
Purpose of the Study:
- To investigate the impact of maternal hypothyroxinemia on postnatal lung development in Sprague Dawley rats.
- To understand the molecular and structural changes in the lungs of pups born to hypothyroxinemic mothers.
Main Methods:
- Rats were fed a low-iodine diet to induce hypothyroxinemia.
- Pups from iodine-deficient (ID) and iodine-sufficient (IS) mothers were compared at postnatal days 8 and 16.
- Lung histology, gene expression (thyroid hormone receptor-β, surfactant proteins, MMP-9, TTF-1, SP-D), and lung function tests were performed.
Main Results:
- ID pups exhibited low thyroxine (T4) levels and increased thyroid hormone receptor-β mRNA.
- Histology showed larger, irregular alveoli and reduced lung function (tidal volume, flow rates, compliance) in ID pups.
- Decreased surfactant protein-B and -C (SP-B, SP-C) and matrix metalloproteinase-9 (MMP-9) mRNA levels were observed in ID pups.
Conclusions:
- Maternal hypothyroxinemia results in immature lung development characterized by altered alveolar structure and reduced lung function.
- Lower levels of SP-B and SP-C in ID pups may contribute to impaired lung compliance and respiratory distress.
- This study suggests maternal hypothyroxinemia as a potential factor in high infant mortality observed in iodine-deficient neonates.
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.
