title: Progesterone and heparin-binding epidermal growth factor-like growth factor regulate the expression of tight junction protein Claudin-3 during early pregnancy.
abstract: OBJECTIVE
  To determine Claudin-3 expression and its regulatory factors during embryo implantation.
  
  
  METHODS
  Experimental mouse models and cell culture.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Sexually mature female CD-1 strain mice.
  
  
  METHODS
  Ovariectomy and treatments.
  
  
  METHODS
  In situ hybridization and immunohistochemistry for detecting Claudin-3 messenger RNA and protein expression in mouse uterus, respectively; Western blot for detecting protein levels; immunofluorescence for detecting Claudin-3 protein in cultured cells.
  
  
  RESULTS
  Claudin-3 is strongly expressed in the uterine luminal epithelium on days 3 and 4 of pregnancy, and diminished at day 5 implantation sites. Then it is expressed at secondary decidual zone on day 8. Pseudopregnant uteri have a similar expression pattern as pregnant uteri from days 1-5. Claudin-3 expression is down-regulated after delayed implantation is activated by estrogen (E) treatment. Meanwhile Claudin-3 expression is stimulated by artificial decidualization. In ovariectomized mice, P induces Claudin-3 expression in the luminal epithelium, which is abrogated by P receptor antagonist RU486. Heparin-binding-epidermal growth factor (HB-EGF) down-regulates Claudin-3 expression, but enhances transcription factor Snail expression. In human endometrial epithelial ECC-1 cells, both E and P could stimulate Claudin-3 expression, whereas HB-EGF decreases Claudin-3 and increases Snail expression.
  
  
  CONCLUSIONS
  Claudin-3 expression in uterine luminal epithelium is stimulated by P and suppressed by HB-EGF in mice and humans.
authors.affiliation: Department of Biology, Shantou University, Shantou, People's Republic of China; School of Life Science, Xiamen University, Xiamen, People's Republic of China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liang
authors.forename: Xiu-Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.forename: Qian-Rong
authors.initials: QR
authors.lastname: Qi
authors.forename: Tong-Song
authors.initials: TS
authors.lastname: Wang
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Gu
authors.forename: Zeng-Ming
authors.initials: ZM
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D062465:Claudin-3 / Q000235:genetics / Q000378:metabolism*; D010065:Embryo Implantation, Delayed; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor; D006727:Hormone Antagonists / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
chemical_list: C568122:CLDN3 protein, human; D062465:Claudin-3; C568123:Cldn3 protein, mouse; D004967:Estrogens; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D011980:Receptors, Progesterone; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D011374:Progesterone
keywords: Claudin-3; Uterus; embryo implantation