| 1. |
- Brännström, Mats, 1958, et al.
(författare)
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Transplantation of the uterus.
- 2003
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Ingår i: Molecular and cellular endocrinology. - 0303-7207. ; 202:1-2, s. 177-84
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Forskningsöversikt (refereegranskat)abstract
- Most women with uterine factor infertility have today no prospect of carrying a pregnancy to term. The development of a method for transplantation of the human uterus would be a means for many of these women to become both genetic and gestational mothers. In this article we review the literature concerning the history and recent development in the area of uterine transplantation. We describe our newly developed model for heterotopic uterine transplantation in the mouse, which we are using for studies of pregnancy outcome and rejection mechanisms. We also address some of the specific questions that need to be solved before attempts to transplant the human uterus should be performed.
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| 2. |
- Brännström, Mats, 1958, et al.
(författare)
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Uterine transplantation.
- 2003
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Ingår i: European journal of obstetrics, gynecology, and reproductive biology. - 0301-2115. ; 109:2, s. 121-3
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Forskningsöversikt (refereegranskat)abstract
- Uterine factor infertility is either due to congenital malformation or acquired. Most women with uterine factor infertility have no chance to become genetic mothers, except by the use of gestational surrogacy. The logical but radical approach for treatment would be replacement of the unfunctional or absent uterus. Uterine transplantation could allow these women to become both genetic and gestational mothers. The present work reviews the existing literature on the history and recent development around this topic. We also briefly describe a newly developed model for heterotopic uterine transplantation in the mouse, in which pregnancies have been accomplished. Some specific issues that are required to be solved prior any further attempts to transplant the uterus in humans are also addressed.
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| 3. |
- Racho El-Akouri, Randa, 1971, et al.
(författare)
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Pregnancy in transplanted mouse uterus after long-term cold ischaemic preservation.
- 2003
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Ingår i: Human reproduction (Oxford, England). - 0268-1161. ; 18:10, s. 2024-30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to evaluate the viability of the transplanted murine uterus after cold ischaemic preservation. METHODS: Uteri of mice (6-8 weeks old) were isolated and kept at 4 degrees C in vitro for 24 or 48 h in 0.154 mol/l NaCl or University of Wisconsin (UW) solution. Viability was evaluated by assessment of morphology and contractility in vitro. Furthermore, uteri were transplanted by vascular anastomoses to syngeneic recipients after 24 or 48 h cold ischaemic preservation in UW solution and morphology, blood flow and capacity to implant transferred blastocysts were assessed 2 weeks later. RESULTS: Uteri that had been preserved for 24 h exhibited normal morphology but after 48 h preservation minimal degenerative changes were seen. Spontaneous contractions occurred in uteri after 24 h as well as 48 h cold ischaemic preservation and prostaglandin F(2alpha)-stimulated responses were preserved. Blood flow and morphology were normal 2 weeks after transplantation in uteri preserved for 24 h, while grafts preserved for 48 h had a decreased blood flow and morphology showed total necrosis of the transplants. Transplanted uteri that had been preserved for 24 h developed pregnancies (in five out of six animals) after embryo transfer, with offspring showing normal weight and growth trajectory. CONCLUSIONS: This study shows for the first time that the mouse uterus tolerates cold ischaemic preservation and that pregnancies can be carried in transplanted uteri that have been preserved for 24 h.
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| 4. |
- Racho El-Akouri, Randa, 1971, et al.
(författare)
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Successful uterine transplantation in the mouse: pregnancy and post-natal development of offspring.
- 2003
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Ingår i: Human reproduction (Oxford, England). - 0268-1161. ; 18:10, s. 2018-23
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Tidskriftsartikel (refereegranskat)abstract
- Uterine transplantation could serve as a tool in studies of the physiology of implantation/pregnancy, and is also a possible future treatment for patients with absolute uterine infertility. Here, the first live-born offspring in any uterine transplantation model is reported.
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| 5. |
- Racho El-Akouri, Randa, 1971
(författare)
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Uterus transplantation. An experimental study in the mouse
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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.
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