Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus

Objective: To evaluate the effects of the immunosuppressant tacrolimus on rejection of a transplanted uterus and on uterine expression of markers of inflammation and implantation. Design: Experimental study. Setting: University laboratory. Animal(s): Female rats. Intervention(s): Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment. Main Outcome Measure(s): Gross morphology, histology, density of T-lymphocytes by immunohistochemistry, and mRNA levels of interleukin (IL)-1 alpha, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-kappa B (NF-kappa B) at 14 days' post-transplantation. Result(s): Nontreated uterine grafts showed rejection with necrosis. Sham groups and the tacrolimus-treated transplanted group exhibited normal uterine morphology with low numbers of T-lymphocytes in all uteri except in two out of seven uteri of the tacrolimus-treated transplant group. Uteri of the nontreated transplanted group showed elevated mRNA expression of IL-1 alpha and IP-10 and reduced galectin-1, compared with the tacrolimus-treated transplanted group. There was no difference between any groups concerning uterine expression of LIF, NF-kappa B, IL-15, and CD200. Conclusion(s): Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1 alpha and IP-10 and prevents T-lymphocyte infiltration. (Fertil Steril (R) 2013;99:862-70. (C) 2013 by American Society for Reproductive Medicine.)