It proves that transplanted uteri can harbour pregnancies and provides hope that successful womb transplants will be possible in women in the future.
The team from Sahlgrenska University, Göteborg, are presenting their work this week to the annual meeting of the European Society of Human Reproduction and Embryology in Madrid.
Team leader Professor Mats Brännström told a news briefing today (Tuesday 1 July) that they have developed a technique for transplantation of the uterus from one mouse to another: in each recipient mouse the transplanted uterus was placed alongside the normal uterus, which acted as a control. After transplantation between genetically identical mice the grafted uterus produced pups. The mouse pups had normal body weight, showed normal behaviour and were fertile. Five out of seven uterine grafts that had been preserved in cooling solution for 24 hours before transplantation also produced healthy pups. Transplantation between different strains of mice was also used to study rejection of the transplants.
Professor Brännström said: "There were reports in the 1960s and 1970s of live births from replanted uteri, but these were uteri taken out and replaced in the same animal, so not true transplants. These are the first true transplants in the world to produce live births[1]."
A major difficulty in organ transplantation is the damage caused by ischaemia (bloodlessness) during the time between removing an organ and transplanting it. Organs are therefore preserved in a cooling solution to minimise the problem. No one up to now has investigated the tolerance of uterine tissue to cold ischaemia.
The researchers preserved some of the uteri for 24 hours in UW (University of Wisconsin) solution, which is commonly used to preserve human kidneys, or sodium chloride (NaCL), or for 48 hours in UW solution. They found that the uteri preserved for 24 hours in UW solution still showed normal blood flow and histology two weeks after transplantation, but the graft transplanted after 48 hours showed impaired blood flow and by two weeks was necrotic (had dead tissue).
"What this demonstrates is that in mice, at least, the time limit for removing a uterus and transplanting it is between 24 and 48 hours," said Professor Brännström.
Another major problem in transplantation is organ rejection. This differs between organs depending on the extent of blood vessels, the specific type of cells in the organ and its immune cell population. So, in another study the team investigated what the pattern would be in the uterus, evaluating the transplanted uteri at specific times between day 2 and 28. Rejection progressed gradually from day 2. By day 10 there was severe acute rejection, which showed itself as arthritis and damaged glands. By day 15 there was necrosis and extensive scar tissue.
"The rejection pattern was what we expected – in the vascular 'tree' and the endometrial glands," said Professor Brännström. "There are small differences in the time to rejection and also some small differences in which type of immune cells are active between species such as the mouse and humans. But, there are no mechanistic differences between the mouse and other higher mammals.
"We think our findings have big implications for the development of womb transplants in women. We've demonstrated for the first time that transplanted uteri can harbour pregnancies and that the rejection of the uterus is similar to other organs."
He said further research was needed before moving on to humans – more answers on controlling rejection and on the possible effects of immunosuppression on pregnancies. They had now started this work and were also developing their techniques in pigs.
Womb transplants could help between 3-4% of infertile women, Professor Brännström believes, and could be an alternative to surrogacy. "We estimate that at there are at least a thousand women in this category in Sweden alone. This includes women with congenital malformations, those born without a uterus and those whose uterus is defective because of large leiomyomas[2] or Asherman's Syndrome[3]. It may also benefit women who have lost their uterus because of emergency operations due to post-partum haemorrhage, and those who have had early stage cervical cancer."
Abstract nos: O-159 (Tuesday 16.00hrs CET Madrid room) O-269 (Wednesday 14.45hrs CET Paris room).
[1] Saudi-Arabian researchers last year published that they had transplanted a woman's uterus, but it failed after two cycles because of a block in one of the grafted vessels that cut off the blood supply.
[2] Leiomyomas are benign tumours.
[3] Asherman's Syndrome: the partial or complete obliteration of the uterine cavity by adhesions due to a number of causes, including endometrial infections or over-vigorous curettage after miscarriage or childbirth.
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