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


METHODS
An 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.


RESULTS
Maternal 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.


CONCLUSIONS
These 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.
Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. xuxuefeng@zju.edu.cn.
Xue-Feng
XF
Xu
Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. yaojing755@aliyun.com.
Qiong-Yao
QY
Hu
Department of Pediatric ICU, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. 157004798@qq.com.
Ling-Fang
LF
Liang
Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. zjuent@163.com.
Lei
L
Wu
Department of Pathology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. 1036088646@qq.com.
Wei-Zhong
WZ
Gu
Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. 68733882@qq.com.
Li-Li
LL
Tang
Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. chinafulc@qq.com.
Lin-Chen
LC
Fu
Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People's Republic of China. dulizhong@zju.edu.cn.
Li-Zhong
LZ
Du
D000107:Acetylation; D000367:Age Factors; D000485:Allergens; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D019175:DNA Methylation; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D009752:Nutritional Status; D010047:Ovalbumin; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
D000485:Allergens; D019332:Endothelin-1; D006657:Histones; D010047:Ovalbumin