title: Altered methylation and expression patterns of genes regulating placental angiogenesis in preterm pregnancy.
abstract: BACKGROUND
  Altered angiogenesis has been implicated in the pathogenesis of various pregnancy complications, particularly preeclampsia. At present, there is a lack of data on the possible role of angiogenesis and its molecular mechanism in preterm pregnancy. We have previously reported reduced placental global DNA methylation levels in preterm pregnancy. Now, we have extended the study to examine plasma levels of angiogenic factors from maternal and cord blood and correlate them with placental promoter CpG methylation and messenger RNA expression of these angiogenic genes in preterm pregnancies.
  
  
  METHODS
  We recruited 99 women delivering at term and 90 women delivering preterm. Plasma levels of angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), fms-related tyrosine kinase 1 (FLT-1), and kinase insert domain receptor (KDR) were analyzed by enzyme-linked immunosorbent assay. Expression levels and promoter CpG methylation of angiogenic genes in placentae were determined by quantitative real-time polymerase chain reaction and by the Sequenom EpiTYPER technology, respectively.
  
  
  RESULTS
  Maternal VEGF and PlGF levels (P < .01 for both) were lower but soluble FLT-1 (sFLT-1) levels and sFLT-1-PlGF ratio (P < .05 for both) were higher in the preterm group. Placental VEGF expression (P < .05) was lower, and CpG site 14 in the VEGF promoter was hypermethylated (P < .05) in the preterm group. The KDR expression (P < .05) was higher in women delivering preterm.
  
  
  CONCLUSIONS
  Our study provides first evidence of differential placental CpG methylation patterns and expression of VEGF, FLT-1, and KDR genes in women delivering preterm. This may explain the possible mechanism for angiogenic imbalance in the pathophysiology of preterm pregnancy.
authors.affiliation: Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, Maharashtra, India.
authors.forename: Deepali P
authors.initials: DP
authors.lastname: Sundrani
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Andhra Pradesh, India.
authors.forename: Umakar S
authors.initials: US
authors.lastname: Reddy
authors.affiliation: Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, Maharashtra, India.
authors.forename: Preeti M
authors.initials: PM
authors.lastname: Chavan-Gautam
authors.affiliation: Department of Obstetrics and Gynecology, Bharati Medical College and Hospital, Bharati Vidyapeeth University, Pune, Maharashtra, India.
authors.forename: Savita S
authors.initials: SS
authors.lastname: Mehendale
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, Andhra Pradesh, India.
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
authors.affiliation: Department of Nutritional Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, Maharashtra, India srjoshi62@gmail.com.
authors.forename: Sadhana R
authors.initials: SR
authors.lastname: Joshi
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005786:Gene Expression Regulation; D005865:Gestational Age; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics*; D010641:Phenotype; D010920:Placenta / Q000098:blood supply*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood / Q000235:genetics; D047928:Premature Birth / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood; D047929:Term Birth; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: DNA methylation; angiogenic factors; preterm pregnancy