Abstract
Uterus transplantation (UTx) is an option for women with uterine factor infertility to have a child, but is still in the experimental stage. Therefore, allogeneic animal models of UTx are required for resolution of clinical issues. In this study, long-term outcomes were evaluated in four recipients (cases 1–4) after allogeneic UTx in cynomolgus macaques. Immunosuppression with antithymocyte globulin induction and a triple maintenance regimen was used. Postoperative ultrasonography and biopsy of the transplanted uterus and immunoserological examinations were performed. All four recipients survived for >3 months after surgery, but continuous menstruation did not resume, although temporary menstruation occurred (cases 1 and 2). All animals were euthanized due to irreversible rejection and no uterine blood flow (cases 1, 2 and 4) and post-transplant lymphoproliferative disorder (case 3). Donor-specific antibodies against MHC class I and II were detected in cases 1, 2 and 4, but not in case 3. Peripheral lymphocyte counts tended to elevate for CD3+, CD20+ and NK cells in conjunction with uterine rejection, and all animals had elevated stimulation indexes of mixed lymphocyte reaction after surgery. Establishment of allogeneic UTx in cynomolgus macaque requires further exploration of immunosuppression, but the clinicopathological features of uterine rejection are useful for development of human UTx.
Highlights
Uterus transplantation (UTx) has become a potential option for women with uterine factor infertility to have a child
The biopsy included myometrial tissue, which was atrophic and had a small area of hyalinization. These findings indicated at least moderate rejection, and this was improved to mild rejection based on a biopsy on postoperative day (POD) 118
UTx is conducted in humans in several countries, but is still considered to be in the experimental stage since there are remaining clinical and technical issues to be resolved [25]
Summary
Uterus transplantation (UTx) has become a potential option for women with uterine factor infertility to have a child. Data accumulated from animal studies for more than a decade have led to clinical application of UTx. Brännström et al described the first human delivery after UTx with a living donor in 2014 [1] and Ejzenberg et al achieved the first live birth after UTx from a deceased donor in 2017 [2]. Brännström et al described the first human delivery after UTx with a living donor in 2014 [1] and Ejzenberg et al achieved the first live birth after UTx from a deceased donor in 2017 [2] These important achievements have attracted considerable attention worldwide, and many teams have recently aimed for clinical application of UTx with accumulation of basic experimental data. Careful accumulation of data in animal experiments is needed for full establishment of clinical application of UTx because the technology associated with UTx has not been standardized
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