Estrogen induces IDO expression via TGF­ß in chorionic villi and decidua during early stages of pregnancy.

ABSTRACT

Indoleamine 2,3­dioxygenase (IDO) is one of the most important proteins protecting the embryos from the mother's immune system during pregnancy; however, little is known about the regulation of expression of this protein at the maternal­fetal interface. In the current study, chorionic villi and decidua were collected from women at early stages of pregnancy. Samples of chorionic villi and decidua were cultured in medium containing different concentrations of 17ß­estradiol and estriol respectively, with or without fulvestrant. Western blot analysis and/or immunofluorescent staining were used to detect the expression of transforming growth factor ß (TGF­ß) and IDO in chorionic villi and decidua tissues. Both TGF­ß and IDO were expressed in chorionic villi and decidua. The expression levels of these two proteins increased the most in samples of chorionic villi and decidua cultured in medium containing 17ß­estradiol at the concentration of 10 ng/ml, or estriol at the concentration of 1 µg/ml. This increase could be reversed when fulvestrant was added in the medium at the concentration of 10 µg/ml. IDO expression increased in a dose­dependent manner in tissue samples cultured in medium containing TGF­ß. The results of the current study revealed that administration of estrogen at doses similar to those observed in healthy pregnant women may upregulate the expression of IDO by TGF­ß, suggesting that estrogen may prevent allogeneic fetal rejection and may be used as an immunomodulator.