Long-Term Outcome and Rejection After Allogeneic Uterus Transplantation in Cynomolgus Macaques

• Main Authors: Iori Kisu, Hirohito Ishigaki, Katsura Emoto, Yojiro Kato, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Yohei Masugi, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Hideaki Tsuchiya, Takako Sasamura, Hiroyuki Urano, Masatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa, Takashi Shiina
• Format: Article
• Language: English
• Published: MDPI AG 2019-10-01
• Series: Journal of Clinical Medicine
• Subjects: uterus transplantation; uterine transplantation; cynomolgus macaque; uterine factor infertility; allogeneic uterus transplantation; rejection
• Online Access: https://www.mdpi.com/2077-0383/8/10/1572

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.