Estrogen induces indoleamine 2,3-dioxygenase expression via suppressors of cytokine signaling 3 in the chorionic villi and decidua of women in early pregnancy.

ABSTRACT

PROBLEM: Indoleamine 2,3-dioxygenase (IDO) is a key protein that participates in the protection of embryos against the mother's immune system during pregnancy. How the expression of this protein is regulated at the maternal-fetal interface remains largely unknown. METHOD OF STUDY The chorionic villi and decidua of women in early pregnancy were collected. Tissue explants of the chorionic villi and decidua were cultured in media containing varying concentrations of 17ß-estradiol and estriol with or without fulvestrant. Western blot analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expression of IDO and the suppressors of cytokine signaling 3 (SOCS3) in the cultured tissues from chorionic villi and decidua. RESULTS: Both IDO and SOCS3 were expressed in chorionic villi and decidua. The expression of IDO was increased in tissue explants from chorionic villi and decidua cultured in medium containing different concentrations of 17ß-estradiol or estriol, and this increase was reversed when fulvestrant was added to the medium. The expression of IDO was upregulated, and SOCS3 expression was downregulated the most in tissue explants from chorionic villi and decidua that were cultured in medium containing 17ß-estradiol at a concentration of 10 ng/mL or estriol at a concentration of 1 µg/mL. This increase in IDO and decrease in SOCS3 were reversed when fulvestrant was added to the medium at a concentration of 10 µg/mL. CONCLUSION: At a concentration similar to that present during pregnancy, estrogen may upregulate the expression of IDO via downregulating SOCS3, which implies that estrogen may contribute to the prevention of allogeneic fetal rejection, and further studies may strengthen the possibility of using estrogen as an immune modulator.