Modified uterine allotransplantation and immunosuppression procedure in the sheep model

PLoS One. 2013 Nov 22;8(11):e81300. doi: 10.1371/journal.pone.0081300. eCollection 2013.

Abstract

Objective: To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model.

Methods: In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.

Results: Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis.

Conclusion: We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Graft Survival
  • Immunosuppression / methods*
  • Organ Transplantation / methods*
  • Postoperative Care
  • Sheep
  • Transplantation, Homologous
  • Uterus / transplantation*

Grant support

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81001161 and 81271070). The funder of Nos. 81001161 had role in study design, data collection, decision to publish, and preparation of the manuscript. The funder of Nos. 81271070 had role in data analysis, decision to publish, and preparation of the manuscript.