Embryo

Cyclosporin A Improves Pregnant Outcome by Promoting Functions of Trophoblasts and Inducing Maternal Tolerance to the Allogeneic Fetus

Abstract
The embryo expresses paternal antigens foreign to mother, and therefore has been viewed as a natural allograft. Cyclosporin A, CsA, is an immunosuppressant for preventing from allograft rejection. Little is known, however, about the modulating effect of CsA on the materno-fetal relationship. In this study, pregnant CBA/J females mated with DBA/2 or BALB/c males as abortion-prone and normal pregnancy matings were administered, respectively, with CsA at day 4 of gestation. We demonstrated that the administration of CsA at the window of implantation resulted in maternal T cell tolerance to paternal antigen, and improved pregnant outcome in the CBA/JxDBA/2 abortion-prone matings. The CsA administration enhanced Th2, reduced Th1 cytokine production at the materno-fetal interface, and expanded peripheral CD4+CD25+ FOXP3+ regulatory T cells in abortion-prone matings, implying development of Th2 bias and regulatory T cells. On the other hand, we observed that treatment with CsA leaded to an enhanced growth and invasiveness of trophoblasts in the abortion-prone matings. Together, these findings indicate that CsA in lower dosage can induce materno-fetus tolerance and improve the biological functions of trophoblast cells in the abortion-prone matings, leading to a successful pregnancy, which is useful in clinical therapeutics of spontaneous pregnancy wastage and other pregnant complications.

Key words: Immunology • Pregnancy • Cytokines • Placenta • Trophoblast

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