title: Epigenetic changes in peripheral leucocytes as biomarkers in intrauterine growth retardation rat.
abstract: Epigenetics plays an important role in the fetal origins of adult disease. Intrauterine growth retardation (IUGR) can cause increased histone acetylation of the endothelin-1 (ET-1) gene from pulmonary vascular endothelial cells or the whole lung tissue and persist into later life, likely resulting in increased risk of pulmonary hypertension or asthma later in life. However, little is known regarding the correlation of epigenetic changes between specific tissue and peripheral leucocytes. In the present study, an IUGR rat model was established by maternal nutrient restriction. Peripheral blood leucocytes were isolated to detect theET-1expression level. Chromatin immunoprecipitation was used to analyze histone modification of theET-1gene promoter. TheET-1protein expression of leucocytes from the 1-week IUGR group was similar to that from the 1-week control group.ET-1protein expression of leucocytes from 10-week IUGR rats was obviously higher than that of the other groups (P<0.05). The levels of acetylated histone H3 in theET-1promoter of leucocytes from the 1-week IUGR rats were significantly higher than those from the age-matched control group (P=0.004). Furthermore, the trends continued ≤10 weeks after birth. In conclusion, epigenetic modifications of leucocytes can in part reflect the epigenetic changes of lung tissue in IUGR rats. Epigenetics of peripheral leucocytes may be used as a biomarker for predicting the risk of the development of disease, and may be used as a surrogate to investigate the subsequent development of pulmonary vascular disease or asthma.
authors.affiliation: Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Xu
authors.affiliation: Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Lin-Cheng
authors.initials: LC
authors.lastname: Fu
authors.affiliation: Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Qiong-Yao
authors.initials: QY
authors.lastname: Hu
authors.affiliation: Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Neonatology, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310052, P.R. China.
authors.forename: Li-Zhong
authors.initials: LZ
authors.lastname: Du
keywords: endothelin-1; epigenetics; intrauterine growth retardation; leucocytes