Progesterone and heparin binding epidermal growth factor like growth factor regulate the expression of tight junction protein Claudin 3 during early pregnancy

The spatiotemporal expression and regulatory patterns of the tight junction protein Claudin-3 during embryo implantation using mouse and cell culture models.

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Xuan Liang, M.S., Xiu-Hong Zhang, Ph.D., Bing-Chen Han, Ph.D., Wei Lei, Ph.D., Qian-Rong Qi, M.S., Tong-Song Wang, M.S., Xiao-Wei Gua, Zeng-Ming Yang, Ph.D.

Volume 100, Issue 5, Pages 1410-1418, November 2013



To determine Claudin-3 expression and its regulatory factors during embryo implantation.


Experimental mouse models and cell culture.


University research laboratory.


Sexually mature female CD-1 strain mice.


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.


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.


Claudin-3 expression in uterine luminal epithelium is stimulated by P and suppressed by HB-EGF in mice and humans.

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