Abstract
Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11–19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans.
Highlights
Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment
The primary objective of the www.nature.com/scientificreports animal work included in this study was to investigate this using a model which has already demonstrated a number of the cardiovascular risk factors associated with poor fetal growth[15,16], Since Rho A has been implicated in bronchial hyper-responsiveness in mouse models[17], rat models[18] and humans[19,20] a secondary objective was to use the animal model to explore whether Rho A, and associated kinases ROCK1 and ROCK2 may be sensitive to developmental stress and serve as a link between adverse factors in the fetal environment and later bronchial hyperreactivity (BHR)
We demonstrated an inverse association between abdominal circumference growth between 11 and 19 weeks’ gestation and BHR measured in 6-yearold children
Summary
Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Following from early observations of increased chronic obstructive pulmonary disease in adults who were of low birthweight[5], studies linking faltering fetal growth to wheeze in childhood have provided further evidence that early environmental factors can influence respiratory development[6,7]. These epidemiological observations do not provide information about underlying pathophysiological mechanisms; to understand these, animal models of fetal growth restriction are required[8]. To test the relevance of factors affecting fetal growth to human respiratory development, we analysed data from an epidemiological cohort where both detailed prenatal ultrasound measurements and childhood BHR measurements are available
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