Progesterone modulates CD4+CD25+FoxP3+ regulatory T Cells and TGF‐β1 in the maternal‐fetal interface of the late pregnant mouse.

Objective: Progesterone supplementation is recommended to prevent spontaneous preterm birth (sPTB) in clinical practice. However, the exact mechanism is still unclear. This study aims to better understand the mechanisms that progesterone can prevent PTB. Methods: Late pregnant mice were given various doses of progesterone receptor antagonist mifepristone, and pregnancy outcomes were observed. Then, non‐pregnant and pregnant mice were given a subcutaneous injection of 40 mg/kg progesterone and 5 mg/kg mifepristone, respectively. CD4+CD25+FoxP3+ Treg cells in peripheral blood and decidua basalis were detected by FACS. Expressions of FoxP3 and TGF‐β1 in the decidua basalis were detected. Results: Mifepristone induced preterm birth, and an obvious dose‐response was found. Proportions of CD4+CD25+FoxP3+ Treg cells in the peripheral blood of non‐pregnant mice increased significantly after progesterone injection. CD4+CD25+FoxP3+ Treg cells in the peripheral blood of pregnant mice increased significantly compared with those of non‐pregnant mice. In pregnant mice, mifepristone significantly decreased the proportions of CD4+CD25+FoxP3+ Treg cells in peripheral blood, and reduced proportions of Treg cells at the maternal‐fetal interface and expressions of FoxP3 and TGF‐β1 in the maternal‐fetal interface. Total 40 mg/kg of progesterone did not increase CD4+CD25+FoxP3+ Treg in the peripheral blood of pregnant mice, but increased proportions of Treg cells at the maternal‐fetal interface and up‐regulated FoxP3 and TGF‐β1 expressions in the maternal‐fetal interface. Conclusion: Progesterone promotes pregnancy immune homeostasis by up‐regulating Treg cells and TGF‐β1 expression in the maternal‐fetal interface. It may be one of the mechanisms of progesterone in preventing sPTB. [ABSTRACT FROM AUTHOR]