title: Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis.
abstract: OBJECTIVE
  The purpose of the present study was to investigate the epigenetic mechanisms responsible for the aberrant aromatase expression (CYP19A1) in Cumulus Cells (CCs) of infertile endometriosis patients.
  
  
  METHODS
  Cumulus cells were obtained from 24 infertile patients with and without endometriosis who underwent ovarian stimulation for intracytoplasmic sperm injection. Expression of CYP19A1 gene was quantified using Reverse Transcription Q-PCR. DNA methylation, histone modifications, and binding of Estrogen Receptor, ERβ to regulatory DNA sequences of CYP19A1 gene were evaluated by Chromatin ImmunoPrecipitation (ChIP) assay.
  
  
  RESULTS
  CYP19A1 gene expression in CCs of endometriosis patients was significantly lower than the control group (P = 0.04). Higher incorporation of MeCP2 (as a marker of DNA methylation) on PII and PI.4 promoters, and hypoacetylation at H3K9 in PII and hypermethylation at H3K9 in PI.4 were observed in CYP19A1 gene in endometriosis patients (P < 0.05). Moreover, a decreased level of ERβ binding to PII and an increased level of its binding to PI.3 and PI.4 promoters of CYP19A1 were observed in endometriosis patients when compared to control.
  
  
  CONCLUSIONS
  Significant reduction of CYP19A1 gene expression in CCs of endometriosis patients may be the result of epigenetic alterations in its regulatory regions, either by DNA methylation or histone modifications. These epigenetic changes along with differential binding of ERβ (as a transcription factor) in CYP19A1 promoters may impair follicular steroidogenesis, leading to poor Oocyte and embryo condition in endometriosis patients.
authors.affiliation: Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Hemmat highway, Tehran, 1449614525, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Hosseini
authors.affiliation: Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Hemmat highway, Tehran, 1449614525, Iran. femehra@yahoo.com.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Mehraein
authors.affiliation: Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 1665659911, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shahhoseini
authors.affiliation: Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 1665659911, Iran.
authors.forename: Leili
authors.initials: L
authors.lastname: Karimian
authors.affiliation: Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Hemmat highway, Tehran, 1449614525, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nikmard
authors.affiliation: Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Number 12, East Hafez Avenue, Bani Hashem Street, Resalat Highway, Tehran, 1665659911, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Ashrafi
authors.affiliation: Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, 1665659911, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Afsharian
authors.affiliation: Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Number 12, East Hafez Avenue, Bani Hashem Street, Resalat Highway, Tehran, 1665659911, Iran. R.aflatoonian@gmail.com.
authors.forename: Reza
authors.initials: R
authors.lastname: Aflatoonian
mesh_terms: D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics*; D003430:Cross-Sectional Studies; D054885:Cumulus Cells / Q000166:cytology*; D019175:DNA Methylation / Q000235:genetics; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D044127:Epigenesis, Genetic / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D042421:Histone Code / Q000235:genetics; D006801:Humans; D007246:Infertility / Q000235:genetics*; D009865:Oocytes / Q000378:metabolism; D010062:Ovulation Induction; D011401:Promoter Regions, Genetic / Q000235:genetics; D020554:Sperm Injections, Intracytoplasmic; D016896:Treatment Outcome
chemical_list: D047629:Estrogen Receptor beta; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: CYP19A1; Cumulus cell; Endometriosis; Epigenetic; Estrogen receptor beta