title: Methylation pattern of H19 exon 1 is closely related to preeclampsia and trophoblast abnormalities.
abstract: Preeclampsia (PE) is a pregnancy-induced disorder characterized by the overproliferation of trophoblasts. Hydatidiform moles, which are associated with a high risk of developing PE, are characterized by the excessive proliferation of trophoblastic tissue. H19 is highly expressed in placental tissue; however, its biological function remains unclear. A fundamental modification of the H19 gene is DNA methylation, which typically occurs in CG-rich regions at the promoter or the first exon region. In this study, in order to investigate the DNA methylation pattern of the H19 exon 1 region in placental tissues and trophoblast cells, placental specimens were collected from women in the first trimester of pregrancy (FTP) and the third trimester of pregnancy (TTP), as well as from from women with severe preeclampsia (sPE). We found that the DNA methylation levels of H19 exon 1 were significantly higher in the tissues obtained from women in TTP than from those obtained from women in FFP. The methylation status of CpG 1 sites within exon 1 of H19 was markedly higher in the placental tissues obtained from women with sPE than in the tissues obtained from women in TTP. In addition, we used the human choriocarcinoma cell line, JEG-3, and treated the cells with the methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza‑Dc). Following treatment with 5-Aza-Dc, the methylation levels at this CpG site showed marked hypomethylation. In addtion, the cell proliferative, migratory and invasive capacities of the cells were remarkably inhibited. Our data suggest that hypermethylation at individual CpG sites within exon 1 of H19 may be involved in the dysfunction of trophoblasts and the pathogenesis of PE.
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Linshan
authors: L
authors: Lu
authors: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Zheng
authors: Z
authors: Hou
authors: Department of Obstetrics and Gynecology, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, Sichuan, P.R. China.
authors: Li
authors: L
authors: Li
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Yanhong
authors: Y
authors: Yang
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Xiaohong
authors: X
authors: Wang
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Beilei
authors: B
authors: Zhang
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Mo
authors: M
authors: Ren
authors: Department of Obstetrics and Gynecology, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, Sichuan, P.R. China.
authors: Dan
authors: D
authors: Zhao
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Zhuo
authors: Z
authors: Miao
authors: Department of Obstetrics and Gynecology, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, Sichuan, P.R. China.
authors: Lili
authors: L
authors: Yu
authors: Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China.
authors: Yuanqing
authors: Y
authors: Yao
mesh_terms: D000328:Adult; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D005091:Exons / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D010920:Placenta / Q000187:drug effects / Q000378:metabolism; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine