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Background: The immunologic factors are the chief reason for recurrent pregnancy loss (RPL) and induction ofmaternal-fetal tolerance is the main treatment for this cause of RPL, but the effect of this method is uncertainly andneeds multiple doses and/or interventions. The aim of this study was to investigate whether a single administrationof transforming growth factor-β1 (TGF-β1) can improve the pregnancy outcomes of RPL mice and whether theimprovement is cause by TGF-β1 driving the expression of immune tolerance molecule indoleamine 2,3-dioxygenase(IDO).Materials and Methods: In this experimental study, 40 RPL model mice were equally divided into a control group,that received 0.01 M phosphate-buffered saline (PBS), and a treatment group, that received PBS containing 2, 20, and200 ng/ml TGF-β1 via tail vein injection. The mice were sacrificed at 13.5 days of pregnancy and the embryo resorptionrate was determined. The expression of IDO, TGF-β1, and TGF-β3 were detected in the placenta using westernblotting and immunohistochemistry techniques.Results: The expression of IDO was positively correlated with TGF-β1 in the placental tissue of RPL mice (r=0.591,P

Abstract Background IL-6 induces the upregulation of indoleamine 2,3-dioxygenase (IDO1) at the maternal-foetal interface, but the regulation mechanisms of IDO1 by IL-6 at this interface have not been fully understood. Methods Western blotting, qRT–PCR and/or immunohistochemistry were employed to measure the expression of IDO1, IL-6, SHP-1/2, SOCS3 and STAT3/p (STAT3 and pSTAT3) in tissues of chorionic villi and decidua (TCVD) in vivo and in cultured TCVD that were treated with IL-6 in the presence or absence of an IL-6 inhibitor. Results Mutually positive relationships among the protein levels of IL-6, IDO1, SHP-1/2 and STAT3/p was observed, and the expression of IDO1, SHP-1/2 and STAT3/p was increased in a dose-dependent manner in TCVD in vivo and in cultured TCVD treated with IL-6 at increasing concentrations (0–100 ng/ml). The level of IL-6 was negatively related to SOCS3 level in TCVD. The expression of SOCS3 was increased in a dose-dependent manner, and SOCS3 level was positively correlated with SHP-1, SHP-2 and STAT3/p level in cultured TCVD treated with 0–2 ng/ml IL-6; however, opposite results were observed after treatment with 2–100 ng/ml IL-6. The IL-6-induced upregulation of IDO1, SHP-1, SHP-2 and STAT3/p expression could be reversed, while the IL-6-induced upregulation of SOCS3 expression was exacerbated by Corylifol A. Conclusions In normal pregnancy, IL-6 upregulates the expression of IDO1 by promoting SHP-1/2 expression via STAT3/p and simultaneously negatively regulates the expression of SOCS3. High expression of IL-6 causes the upregulation of IDO1 expression and the downregulation of SOCS-3 expression, which may be beneficial for maintaining immunological tolerance.