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1 May 2007 Cyclosporin A Improves Pregnancy Outcome by Promoting Functions of Trophoblasts and Inducing Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings in the Mouse
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Abstract

The embryo expresses paternal antigens foreign to the mother, and therefore has been viewed as a natural allograft. Cyclosporin A (CsA) is an immunosuppressant for preventing allograft rejection. Little is known, however, about the modulating effect of CsA on the materno-fetal relationship. In this study, pregnant CBA/J female mice mated with DBA/2 or BALB/c male mice 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 it improved pregnancy outcome in the CBA/J ⊠ DBA/2 abortion-prone matings. CsA administration enhanced Th2 and reduced Th1 cytokine production at the materno-fetal interface, and it 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 led to enhanced growth and invasiveness of trophoblasts in the abortion-prone matings. Together, these findings indicate that CsA in lower dosages can induce materno-fetal tolerance and improve the biologic functions of trophoblast cells in the abortion-prone matings, leading to a successful pregnancy, which is useful in clinical therapeutics for spontaneous pregnancy wastage and other pregnancy complications.

Mei-Rong Du, Lin Dong, Wen-Hui Zhou, Feng-Ting Yan, and Da-Jin Li "Cyclosporin A Improves Pregnancy Outcome by Promoting Functions of Trophoblasts and Inducing Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings in the Mouse," Biology of Reproduction 76(5), 906-914, (1 May 2007). https://doi.org/10.1095/biolreprod.106.056648
Received: 22 August 2006; Accepted: 1 January 2007; Published: 1 May 2007
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