6533b824fe1ef96bd12801d2

RESEARCH PRODUCT

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

Cesar Diaz-garciaCesar Diaz-garciaJohan MölneMats BrännströmRanda Racho El-akouriShamima N. AkhiCaiza A. Wranning

subject

Graft Rejectionmedicine.medical_specialtyNecrosisGalectin 1UterusHysterectomyTacrolimusAndrologyNecrosisInterleukin-1alphaRats Inbred BNInternal medicineUterus transplantationmedicineAnimalsTransplantation HomologousInflammationbusiness.industryUterusObstetrics and GynecologyInterleukinHistologyOrgan TransplantationTacrolimusRatsChemokine CXCL10Transplantationsurgical procedures operativeEndocrinologymedicine.anatomical_structureReproductive MedicineRats Inbred LewFemalemedicine.symptombusinessLeukemia inhibitory factorBiomarkersImmunosuppressive Agents

description

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)-1α, leukemia inhibitory factor (LIF), galectin-1, CD200, IL-15, interferon-inducible protein-10 (IP-10), and nuclear factor-κB (NF-κB) 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-1α 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-κB, IL-15, and CD200. Conclusion(s) Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.

https://doi.org/10.1016/j.fertnstert.2012.11.002