Epigenetics of hyper-responsiveness to allergen challenge following intrauterine growth retardation rat.

Xue-Feng Xu,Ling-Fang Liang,Li-Zhong Du,Lei Wu,Li-Li Tang,Wei-Zhong Gu,Qiong-Yao Hu,Lin-Chen Fu

doi:10.1186/s12931-014-0137-7

Xue-Feng Xu, Ling-Fang Liang + Show 6 more

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https://doi.org/10.1186/s12931-014-0137-7

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Abstract

BackgroundEpidemiological studies have revealed that intrauterine growth retardation (IUGR) or low birth weight is linked to the later development of asthma. Epigenetic regulatory mechanisms play an important role in the fetal origins of adult disease. However, little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR.MethodsAn IUGR and ovalbumin (OVA)-sensitization/challenge rat model was used to study whether epigenetic mechanisms play a role in the development of asthma following IUGR.ResultsMaternal nutrient restriction increased histone acetylation levels of the endothelin-1 (ET-1) gene promoter in lung tissue of offspring, but did not cause significant alterations of DNA methylation. The effect was maintained until 10 weeks after birth. Furthermore, these epigenetic changes may have induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma.ConclusionsThese findings suggest that epigenetic mechanisms might be closely associated with the development of asthma following IUGR, providing further insight for improved prevention of asthma induced by environmental factors.

Highlights

An adverse intrauterine environment, such as that resulting from maternal malnutrition, may impact the development of the fetus resulting in fetal growth restriction or intrauterine growth retardation (IUGR) [1,2]
In other CpG sites, no significant differences were observed. These results show that intrauterine malnutrition was not sufficient to cause a significant change in DNA methylation of the ET-1 gene
These epigenetic changes induced IUGR individuals to be highly sensitive to OVA challenge later in life, resulting in more significant changes related to asthma

Summary

Introduction

An adverse intrauterine environment, such as that resulting from maternal malnutrition, may impact the development of the fetus resulting in fetal growth restriction or intrauterine growth retardation (IUGR) [1,2]. A study by Villamor et al indicated that low birth weight was associated with a significantly greater risk of asthma independent of gestational age, sex, year of birth, or maternal age, parity, or socioeconomic status; among monozygotic twins, birth weight less than 2500 g was related to increased risks of asthma [12]. These investigations further revealed that, in addition to shared environmental or genetic factors, other regulatory mechanism such as DNA methylation or histone modifications might be involved in the development of asthma following either IUGR or low birth weight. Little is known regarding the correlation between epigenetic regulation and the development of asthma following IUGR

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