Effects of immunosuppression by cyclosporine A on allogenic uterine transplant in the rat

Objective(s): Research on uterine transplantation (UTx) is conducted in preparation for its introduction in the human as a treatment for absolute uterine factor infertility. A major area of research in experimental animals is to ascertain that immunosuppressants that will be used at UTx do not negatively affect the potential of the uterus to implant an embryo and to carry a pregnancy to term. This study investigates the effects on a uterine transplant in the rat of the calcineurin inhibitor, cyclosporine A (CsA), on uterine morphology and expression patterns of some mediators involved in implantation/inflammation.Study design: Donor rats were of Brown Norway strain and recipients were of Lewis strain. The uterus was transplanted to an orthotopic site by vascular anastomosis. The recipients were given CsA (10 mg/kg) sc once daily or no CsA until they were sacrificed at postoperative day 7. Syngenic transplanted Lewis rats were used as controls. Uteri were analyzed regarding histology, immunohistochemistry against T-cells and mRNA levels of the implantation/inflammation-related markers leukaemia inhibitory factor (LIF), galectin-1, CD200, interleukin (IL)-1α, and IL-15.Result(s): There was pronounced inflammation with abundance of CD8-lymphocytes in uterine grafts of non-CsA-treated animals and only mild inflammation in treated animals. The uterine mRNA levels of IL-1α were decreased after CsA in comparison to uteri of non-treated transplanted animals. The mRNA levels of galectin-1 were decreased in the rejected uteri and were higher in the CsA-treated. The levels of mRNA of IL-15 were lower in the syngenic transplanted group compared to the CsA-treated transplanted. There was no difference between the groups concerning mRNA levels of CD200, or LIF, with wide variation of the levels of the two latter mediators in all groups.Conclusion(s): Cyclosporine A suppresses rejection of an allogenic rat uterine transplant, with normalization of mRNA levels of the proinflammatory cytokine IL-1α and the glycan-binding protein galectin-1.