Cyclosporin A Improves Pregnancy Outcome by Promoting Functions of Trophoblasts and Inducing Maternal Tolerance to the Allogeneic Fetus in Abortion-Prone Matings in the Mouse1

• Published in: Biology of reproduction 2007-05, Vol.76 (5), p.906-914
• Main Authors: Du, Mei-Rong, Dong, Lin, Zhou, Wen-Hui, Yan, Feng-Ting, Li, Da-Jin
• Format: Article
• Language: English
• Subjects: cytokines; immunology; placenta; pregnancy; trophoblast
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.106.056648

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.