title: Epigenetic regulation of STAT5A and its role as fetal DNA epigenetic marker during placental development and dysfunction.
abstract: Development of normal placenta requires regulated apoptosis of trophoblasts. However, uncontrolled apoptosis has been seen in the pregnancy related complications like hydatidiform mole and pre-eclampsia. STAT5A is a transcription factor with well-known anti-apoptotic role. Thus, we sought to study the role of STAT5A and its epigenetic regulation in placental development and pathologies and its use as fetal DNA epigenetic marker.
  
  
  
  The present study was conducted on pregnant women who were enrolled in five groups, based on the three trimesters in normal pregnancy and two pregnancy related disorder groups: pre-eclampsia and hydatidiform mole. Placental villi samples and maternal blood were obtained from each pregnant woman and were analyzed for promoter region methylation (via methylation sensitive high resolution melting) and histone trimethylations (via chromatin immunoprecipitation) of STAT5A.
  
  
  
  Our data revealed higher expression of STAT5A in first trimester villi, which decreased with advancing gestation with corresponding increased DNA methylation and H3 trimethylations. Development of choriocarcinoma was associated with DNA methylation associated lower expression of STAT5A. The pattern of promoter methylation of STAT5A in cell free DNA within maternal plasma was observed to be similar to its promoter methylation in placental villi during normal pregnancy, pre-eclampsia and molar complications, which suggested its use as a novel fetal DNA epigenetic marker.
  
  
  
  Our results suggest the regulation of STAT5A via epigenetic mechanisms during normal pregnancy and the association of STAT5A epigenetic dysregulation in pregnancy related complications. Further, hypermethylated STAT5A can be utilized as novel fetal DNA epigenetic marker.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Beenish
authors.initials: B
authors.lastname: Rahat
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Thakur
authors.affiliation: Department of Obstetricsand Gynaecology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Bagga
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: jyotdeep2001@yahoo.co.in.
authors.forename: Jyotdeep
authors.initials: J
authors.lastname: Kaur
mesh_terms: D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002824:Chorionic Villi / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000378:metabolism*; D010929:Placentation / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D050799:STAT5 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins
keywords: Epigenetic regulation; Hydatidiform mole; Placenta; Pre-eclampsia; STAT5A