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

Fertil Steril. 2013 Mar 1;99(3):862-70. doi: 10.1016/j.fertnstert.2012.11.002. Epub 2012 Dec 4.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Chemokine CXCL10 / metabolism
  • Female
  • Galectin 1 / metabolism
  • Graft Rejection / drug therapy*
  • Graft Rejection / pathology
  • Hysterectomy
  • Immunosuppressive Agents / pharmacology*
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Interleukin-1alpha / metabolism
  • Necrosis
  • Organ Transplantation / methods*
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Tacrolimus / pharmacology*
  • Transplantation, Homologous
  • Uterus / transplantation*

Substances

  • Biomarkers
  • Chemokine CXCL10
  • Cxcl10 protein, rat
  • Galectin 1
  • Immunosuppressive Agents
  • Interleukin-1alpha
  • Tacrolimus