Uterus transplantation. An experimental study in the mouse

Abstract

Uterus transplantation is a possible future treatment for uterine factor infertility, which can be either congenital (uterus agenesis/hypoplasia) or acquired (hysterectomy or intrauterine adhesions). The present study represents experiments where an animal model for uterine transplantation was developed and characterized. Initially, a method for heterotopic uterine transplantation in the mouse was developed. The experiments involved syngeneic transplantation of the uterine horn placed alongside the native uterus. Vascular connections were accomplished by end-to-side anastomoses of aorta/aorta and vena cava/vena cava. There was a typical learning curve of the procedure, with the success rate increasing with experience. Histological evaluation showed that the transplanted uterus was well preserved and the blood flow was similar to that of the native uterus. In one animal, embryos were transferred into the transplanted uterus and pregnancy occurred. This is the first time pregnancy has been shown in a transplanted mouse uterus.The model was modified to include a cervical cutaneous stoma of the transplanted uterus and the implantation rate was thereby increased. In a detailed study of pregnancy in the transplanted uteri it was shown that implantation and pregnancy rates were similar to the native uteri of the transplanted animals and to control animals. Furthermore, offspring from transplanted uteri developed normally and were fertile. This study shows that transplanted uteri can harbour pregnancies until term and that offspring develop fully normally in a syngeneic setting. A crucial aspect in organ transplantation is the preservation of the graft ex vivo. To test the tolerance of the uterus to cold ischemia, mouse uteri were removed and kept at 4oC in preservation solution for 24 or 48 h. It was shown that the uterus was well preserved after 24 h and could be transplanted to a donor with preserved functionality, which was proven by the ability to implant embryos and to carry a normal pregnancy. The behaviour of the transplanted murine uterus in an allogeneic setting was tested. Uteri of BALB/c mice were transplanted into C57BL/6 recipients. It was shown that the blood flow in the grafted uteri was reduced already after 2 days with a continuous decrease after that. The transplanted uteri showed slight inflammatory changes at 2 days and after 5 days rejection was obvious. At 10 days severe rejection was seen and after 15 days the transplants were necrotic. The study shows that the time frame for the rejection and the mechanisms for rejection of the uterus are similar to that of other parenchymal organs.In summary, this study has shown that a mouse animal model can be used for experimental studies on uterine transplantation. It shows for the first time pregnancies and normal offspring in a uterus transplantation model. Moreover, the studies show that the uterus is a fairly tolerable organ, which can be preserved for at least 24 h under cold ischemic conditions, and that rejection is similar to that of other transplanted organs.