First Successful Delivery after Uterus Transplantation in MHC-Defined Cynomolgus Macaques

Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globul...

Full description

Bibliographic Details
Main Authors: Iori Kisu, Yojiro Kato, Yohei Masugi, Hirohito Ishigaki, Yohei Yamada, Kentaro Matsubara, Hideaki Obara, Katsura Emoto, Yusuke Matoba, Masataka Adachi, Kouji Banno, Yoko Saiki, Takako Sasamura, Iori Itagaki, Ikuo Kawamoto, Chizuru Iwatani, Takahiro Nakagawa, Mitsuru Murase, Hideaki Tsuchiya, Hiroyuki Urano, Masatsugu Ema, Kazumasa Ogasawara, Daisuke Aoki, Kenshi Nakagawa, Takashi Shiina
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/9/11/3694
Description
Summary:Delivery following uterus transplantation (UTx)—an approach for treating uterine factor infertility—has not been reported in nonhuman primate models. Here, six female major histocompatibility complex (MHC)-defined cynomolgus macaques that underwent allogeneic UTx were evaluated. Antithymocyte globulin and rituximab were administered to induce immunosuppression and a triple maintenance regimen was used. Menstruation resumed in all animals with long-term survival, except one, which was euthanized due to infusion associated adverse reaction to antithymocyte globulin. Donor-specific antibodies (DSA) were detected in cases 2, 4, and 5, while humoral rejection occurred in cases 4 and 5. Post-transplant lymphoproliferative disorder (PTLD) developed in cases 2 and 3. Pregnancy was attempted in cases 1, 2, and 3 but was achieved only in case 2, which had haploidentical donor and recipient MHCs. Pregnancy was achieved in case 2 after recovery from graft rejection coincident with DSA and PTLD. A cesarean section was performed at full-term. This is the first report of a successful livebirth following allogeneic UTx in nonhuman primates, although the delivery was achieved via UTx between a pair carrying haploidentical MHCs. Experimental data from nonhuman primates may provide important scientific knowledge needed to resolve unsolved clinical issues in UTx.
ISSN:2077-0383