Effect of Exogenous of Transforming Growth Factor-β1 on Pregnancy Outcome in Mice with Recurrent Pregnancy Loss by Persistent Enhancement of Placental Tissue Indoleamine 2,3-Dioxygenase Expression.

BACKGROUND

The immunologic factors are the chief reason for recurrent pregnancy loss (RPL) and induction of maternal-fetal tolerance is the main treatment for this cause of RPL, but the effect of this method is uncertainly and needs multiple doses and/or interventions. The aim of this study was to investigate whether a single administration of transforming growth factor-β1 (TGF-β1) can improve the pregnancy outcomes of RPL mice and whether the improvement 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, and 200 ng/ml TGF-β1 via tail vein injection. The mice were sacrificed at 13.5 days of pregnancy and the embryo resorption rate was determined. The expression of IDO, TGF-β1, and TGF-β3 were detected in the placenta using western blotting 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<0.001). In all treatment groups, the embryo resorption rates were significantly lower than the control group and the expression of IDO in the placental tissue of all treatment groups was significantly higher than the control group. The expression of TGF-β1 increased gradually from, 2, 20 to 200 ng/ml in treatment groups, and the concentration of exogenous TGF-β1 positively correlated with the expression of TGF-β1, in placental tissues in treatment groups (r=0.372, P=0.018).

CONCLUSION

Exogenous TGF-β1 improves pregnancy outcomes in RPL mice, and the possible therapeutic mechanism is that exogenous TGF-β1 induces the persistent expression of endogenous TGF-β1 and IDO due to mutually induced expression of the other. This experiment may provide a new direction and idea for the future treatment of RPL patients.