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

Hum Reprod. 2017 Oct 1;32(10):2026-2035. doi: 10.1093/humrep/dex250.


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.

Study funding/competing interest(s): This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 26713050. None of the authors has a conflict of interest to declare.

Keywords: cynomolgus macaque; ischemia and reperfusion injury; uterine factor infertility; uterus transplantation; warm ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Animals
  • Blood Gas Analysis
  • Female
  • Humans
  • Infertility, Female / surgery
  • Lactic Acid / blood
  • Macaca fascicularis
  • Menstruation
  • Models, Animal
  • Optical Imaging
  • Potassium / blood
  • Reperfusion Injury / pathology*
  • Time Factors
  • Ultrasonography
  • Uterus / diagnostic imaging
  • Uterus / pathology
  • Uterus / transplantation*
  • Warm Ischemia*


  • Lactic Acid
  • Potassium