Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: A basic study for uterus transplantation

Iori Kisu, Kiyoko Umeneo, Masataka Adachi, Katsura Emoto, Yuya Nogami, Kouji Banno, Iori Itagaki, Ikuo Kawamoto, Takahiro Nakagawa, Hayato Narita, Atsushi Yoshida, Hideaki Tsuchiya, Kazumasa Ogasawara, Daisuke Aoki

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

STUDY QUESTION: How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? SUMMARY ANSWER: Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. WHAT IS KNOWN ALREADY: Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. STUDY DESIGN, SIZE, DURATION: This experimental study included 18 female cynomolgus macaques with periodic menstruation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Animals were divided into six groups of three monkeys each: A control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. LIMITATIONS, REASON FOR CAUTION: Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to humans. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that the tolerable warm ischemia time in the uterus is expected to be longer than that in other vital organs.

Original languageEnglish
Pages (from-to)2026-2035
Number of pages10
JournalHuman Reproduction
Volume32
Issue number10
DOIs
Publication statusPublished - 2017 Oct 1

Fingerprint

Warm Ischemia
Macaca
Reperfusion Injury
Uterus
Transplantation
Reperfusion
Menstruation
Ischemia
Primates
Infertility
Haplorhini
Biopsy

Keywords

  • cynomolgus macaque
  • ischemia and reperfusion injury
  • uterine factor infertility
  • uterus transplantation
  • warm ischemia

ASJC Scopus subject areas

  • Reproductive Medicine
  • Rehabilitation
  • Obstetrics and Gynaecology

Cite this

Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque : A basic study for uterus transplantation. / Kisu, Iori; Umeneo, Kiyoko; Adachi, Masataka; Emoto, Katsura; Nogami, Yuya; Banno, Kouji; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Narita, Hayato; Yoshida, Atsushi; Tsuchiya, Hideaki; Ogasawara, Kazumasa; Aoki, Daisuke.

In: Human Reproduction, Vol. 32, No. 10, 01.10.2017, p. 2026-2035.

Research output: Contribution to journalArticle

Kisu, I, Umeneo, K, Adachi, M, Emoto, K, Nogami, Y, Banno, K, Itagaki, I, Kawamoto, I, Nakagawa, T, Narita, H, Yoshida, A, Tsuchiya, H, Ogasawara, K & Aoki, D 2017, 'Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: A basic study for uterus transplantation', Human Reproduction, vol. 32, no. 10, pp. 2026-2035. https://doi.org/10.1093/humrep/dex250
Kisu, Iori ; Umeneo, Kiyoko ; Adachi, Masataka ; Emoto, Katsura ; Nogami, Yuya ; Banno, Kouji ; Itagaki, Iori ; Kawamoto, Ikuo ; Nakagawa, Takahiro ; Narita, Hayato ; Yoshida, Atsushi ; Tsuchiya, Hideaki ; Ogasawara, Kazumasa ; Aoki, Daisuke. / Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque : A basic study for uterus transplantation. In: Human Reproduction. 2017 ; Vol. 32, No. 10. pp. 2026-2035.
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AU - Adachi, Masataka

AU - Emoto, Katsura

AU - Nogami, Yuya

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AU - Itagaki, Iori

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AU - Nakagawa, Takahiro

AU - Narita, Hayato

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N2 - STUDY QUESTION: How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? SUMMARY ANSWER: Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. WHAT IS KNOWN ALREADY: Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. STUDY DESIGN, SIZE, DURATION: This experimental study included 18 female cynomolgus macaques with periodic menstruation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Animals were divided into six groups of three monkeys each: A control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. LIMITATIONS, REASON FOR CAUTION: Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to humans. WIDER IMPLICATIONS OF THE FINDINGS: The findings suggest that the tolerable warm ischemia time in the uterus is expected to be longer than that in other vital organs.

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