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D Chen1 , P Ganapathy1 , LJ Zhu1 , X Xu1 , Q Li1 , MK Bagchi1 , IC Bagchi1
Population Council and The Rockefeller University, New York, New York 1
The steroid hormone estrogen (E) profoundly influences the early events in the uterus leading to embryo implantation. It is thought that E triggers the expression of a unique set of genes in the endometrium that in turn control implantation. To identify these E-induced genes, we utilized a delayed implantation model system in which embryo attachment to uterus is dependent on E administration. Using a messenger RNA differential display method, we isolated a number of cDNAs that are up- or down-regulated in response to E. We identified one of these cDNAs as that encoding rab11, a p21ras-like GTP-binding protein (G protein), which functions in the targeting of transport vesicles to the plasma membrane. In normal pregnant rats, rab11 mRNA is expressed at low levels on days 1-2 of pregnancy but its expression is markedly enhanced in the uterine glands between days 3-5 immediately prior to implantation. In ovariectomized rats, the expression of rab11 mRNA is induced in the uterus in response to E. In transient transfection experiments, overexpression of estrogen receptor (ER) or induced rab11 mRNA in Ishikawa endometrial cells in an E-dependent manner. These findings, together with the observation that ER- but not ER- is detected in the glands of the preimplantation uterus, indicate that rab11 is one of the proteins that are specifically induced by E-complexed ER- in rat endometrium at the onset of implantation. Our results imply that E, which induces the synthesis of many growth factors and their receptors, and other secretory proteins that are thought to be critical for implantation, may also facilitate their transport to the membrane and/or secretion by stimulating the expression of rab11, a component of the membrane trafficking pathway.
This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.