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Progesterone and heparin-binding epidermal growth factor-like growth factor regulate the expression of tight junction
Xuan Liang1, Xiu-Hong Zhang, Bing-Chen Han
1Department of Biology, Shantou University, Shantou, People's Republic of China; School of Life Science, Xiamen University, Xiamen, People's Republic of China.
Objective:
To determine Claudin-3 expression and its regulatory factors during embryo implantation.
Design:
Experimental mouse models and cell culture.
Setting:
University research laboratory.
Animal(S):
Sexually mature female CD-1 strain mice.
Intervention(S):
Ovariectomy and treatments.
Main Outcome Measure(S):
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.
Result(S):
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.
Conclusion(S):
Claudin-3 expression in uterine luminal epithelium is stimulated by P and suppressed by HB-EGF in mice and humans.
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