title: Uterine rejection after allogeneic uterus transplantation in the rat is effectively suppressed by tacrolimus.
abstract: 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.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Female rats.
  
  
  METHODS
  Uteri from brown Norway rats were transplanted to Lewis rats, receiving either tacrolimus or no treatment. Sham groups underwent either hemihysterectomy or tacrolimus treatment.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Tacrolimus monotherapy suppresses rejection of an allotransplanted uterus and normalizes the expression of IL-1α and IP-10 and prevents T-lymphocyte infiltration.
authors.affiliation: Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. shamima.akhi@obgyn.gu.se
authors.forename: Shamima N
authors.initials: SN
authors.lastname: Akhi
authors.forename: Cesar
authors.initials: C
authors.lastname: Diaz-Garcia
authors.forename: Randa R
authors.initials: RR
authors.lastname: El-Akouri
authors.forename: Caiza A
authors.initials: CA
authors.lastname: Wranning
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.forename: Mats
authors.initials: M
authors.lastname: Brännström
mesh_terms: D000818:Animals; D015415:Biomarkers; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000378:metabolism; D006084:Graft Rejection / Q000188:drug therapy* / Q000473:pathology; D007044:Hysterectomy; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D053582:Interleukin-1alpha / Q000378:metabolism; D009336:Necrosis; D016377:Organ Transplantation / Q000379:methods*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D014184:Transplantation, Homologous; D014599:Uterus / Q000637:transplantation*
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; C091326:Cxcl10 protein, rat; D037483:Galectin 1; D007166:Immunosuppressive Agents; D053582:Interleukin-1alpha; D016559:Tacrolimus