title: Requirement of heart and neural crest derivatives-expressed transcript 2 during decidualization of human endometrial stromal cells in vitro.
abstract: OBJECTIVE
  To investigate the role of heart and neural crest derivatives-expressed transcript 2 (HAND2) during decidualization of human endometrial stromal cells (ESCs).
  
  
  METHODS
  In vitro experiment.
  
  
  METHODS
  Research laboratory.
  
  
  METHODS
  Twenty-six patients undergoing hysterectomy for benign reasons.
  
  
  METHODS
  ESCs were cultured for 12 days with HAND2 small interfering RNA (siRNA) or nonsilencing RNA during decidualization by medroxyprogesterone acetate (MPA) and E2.
  
  
  METHODS
  Decidualization was monitored by changes in cellular morphology and the expression of several decidual-specific genes.
  
  
  RESULTS
  HAND2 siRNA effectively suppressed HAND2 levels in ESCs after 12 days of E2 + MPA treatment. ESCs cultured with HAND2 siRNA retained a long fibroblast-like shape, whereas the cells cultured with control siRNA transformed into enlarged polygonal cells. Silencing of HAND2 expression significantly reduced connexin-43 involved in the morphologic changes. HAND2 silencing significantly reduced the mRNA levels of fibulin-1, prolactin, tissue inhibitor of metalloproteinase 3, interleukin-15, and forkhead box O1A (FOXO1A), but had no effect on the mRNA levels of dickkopf-1, serum glucocorticoid kinase 1, and insulin-like growth factor-binding protein 5. HAND2 siRNA effectively suppressed the levels of nuclear FOXO1A protein as a regulator of decidualization.
  
  
  CONCLUSIONS
  These results suggest that HAND2 plays a key role in the regulation of progestin-induced decidualization of human ESCs.
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hisayuu
authors.initials: H
authors.lastname: Shindoh
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan. Electronic address: hokada@hirakata.kmu.ac.jp.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishigaki
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D015124:8-Bromo Cyclic Adenosine Monophosphate; D051792:Basic Helix-Loop-Helix Proteins; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D012333:RNA, Messenger; C498765:HAND2 protein, human
keywords: HAND2; Human endometrial stromal cells; decidualization; progestin; siRNA