Uterus allotransplantation in cynomolgus macaque

A preliminary experience with non-human primate models

Iori Kisu, Makoto Mihara, Kouji Banno, Hisako Hara, Yohei Masugi, Jun Araki, Takuya Iida, Yohei Yamada, Yojiro Kato, Takashi Shiina, Nobuhiko Suganuma, Daisuke Aoki

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Aim: Uterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. Methods: Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4°C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. Results: The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. Conclusion: Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required.

Original languageEnglish
Pages (from-to)907-918
Number of pages12
JournalJournal of Obstetrics and Gynaecology Research
Volume40
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Macaca
Tacrolimus
Immunosuppressive Agents
Primates
Uterus
Macaca fascicularis
Menstruation
Recovery of Function
Methylprednisolone
Ambulatory Surgical Procedures
Cervix Uteri
Atrophy
Mycophenolic Acid
Biopsy
Uterine Artery
Infertility
Heparin
Ultrasonography
Ischemia
Transplantation

Keywords

  • Cynomolgus macaque
  • Immunosuppressants
  • Indocyanine green
  • Uterine factor infertility
  • Uterus transplantation

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Medicine(all)

Cite this

Uterus allotransplantation in cynomolgus macaque : A preliminary experience with non-human primate models. / Kisu, Iori; Mihara, Makoto; Banno, Kouji; Hara, Hisako; Masugi, Yohei; Araki, Jun; Iida, Takuya; Yamada, Yohei; Kato, Yojiro; Shiina, Takashi; Suganuma, Nobuhiko; Aoki, Daisuke.

In: Journal of Obstetrics and Gynaecology Research, Vol. 40, No. 4, 2014, p. 907-918.

Research output: Contribution to journalArticle

Kisu, Iori ; Mihara, Makoto ; Banno, Kouji ; Hara, Hisako ; Masugi, Yohei ; Araki, Jun ; Iida, Takuya ; Yamada, Yohei ; Kato, Yojiro ; Shiina, Takashi ; Suganuma, Nobuhiko ; Aoki, Daisuke. / Uterus allotransplantation in cynomolgus macaque : A preliminary experience with non-human primate models. In: Journal of Obstetrics and Gynaecology Research. 2014 ; Vol. 40, No. 4. pp. 907-918.
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abstract = "Aim: Uterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. Methods: Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4°C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. Results: The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. Conclusion: Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required.",
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AU - Araki, Jun

AU - Iida, Takuya

AU - Yamada, Yohei

AU - Kato, Yojiro

AU - Shiina, Takashi

AU - Suganuma, Nobuhiko

AU - Aoki, Daisuke

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AB - Aim: Uterine transplantation (UTx) is a potential option for child-bearing in women with uterine infertility. Recovery of uterine function after allogeneic UTx in non-human primates has not been reported. The objective of this study is to establish the functional uterine transplant model in non-human primates. Methods: Uteri of two cynomolgus monkeys were simultaneously removed, cooled at 4°C and perfused with heparin saline. The uteri were interchanged with each other and then orthotopically transplanted. Immunosuppressive protocols included use of three agents (tacrolimus, mycophenolate mofetil and methylprednisolone) in case 1 and two agents (tacrolimus and methylprednisolone) in case 2. Transabdominal ultrasonography, vaginoscopy and biopsy of the transplanted uterine cervix were routinely conducted to monitor rejection after surgery. Results: The blood concentration of tacrolimus decreased 11 days after surgery and evidence of rejection was found in biopsy of the uterine cervix in both cases. The suspected rejection disappeared 23 days after surgery in case 1 and temporary menstruation resumed at 3 months after surgery. In case 2, blood flow to the uterine artery gradually decreased and the uterus resulted in atrophy due to ischemia, which has been triggered by rejection. Conclusion: Allogeneic UTx in the cynomolgus monkeys resulted in temporary recovery of menstruation with three immunosuppressants and uterine atrophy with two immunosuppressants. This preliminary experience suggests that recovery of uterine function after allogeneic UTx in non-human primates is possible but more experiments are required.

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