title: Progesterone Resistance in Endometriosis Is Modulated by the Altered Expression of MicroRNA-29c and FKBP4.
abstract: Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c.
  
  
  
  To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis.
  
  
  
  MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c.
  
  
  
  Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls.
  
  
  
  Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery.
  
  
  
  We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women.
authors: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan 49503.
authors: Niraj R
authors: NR
authors: Joshi
authors: Huntigton Medicina Reprodutiva, São Paulo 04021-000, Brazil.
authors: Eduardo H
authors: EH
authors: Miyadahira
authors: Department of Obstetrics and Gynecology, University of California, Los Angeles, California 90095.
authors: Yalda
authors: Y
authors: Afshar
authors: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan 49503.
authors: Jae-Wook
authors: JW
authors: Jeong
authors: Department of Obstetrics and Gynecology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.
authors: Steven L
authors: SL
authors: Young
authors: Greenville Hospital System, University of South Carolina School of Medicine, Greenville, South Carolina 29605; and.
authors: Bruce A
authors: BA
authors: Lessey
authors: Discipline of Gynecology, Department of Obstetrics and Gynecology, Hospital das clinicas, faculdade de Medicina, Universidade de São Paulo, São Paulo 01246-903, Brazil.
authors: Paulo C
authors: PC
authors: Serafini
authors: Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, Michigan 49503.
authors: Asgerally T
authors: AT
authors: Fazleabas
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000002:abnormalities*; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010215:Papio; D011374:Progesterone / Q000494:pharmacology*; D011379:Prognosis; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D014591:Uterine Diseases / Q000235:genetics*
chemical_list: D015415:Biomarkers; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D011374:Progesterone; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4