Prolonged Cold Ischemia Did Not Impair Mitochondrial Oxygen Consumption or Reactive Oxygen Species Production in Human Uterine Fundus and Horn Myometrium

Mathilde Pélissié,Olivier Garbin,Angélique Bryand,Fabienne Goupilleau,Isabelle Georg,Anne-Laure Charles,Bernard Geny

doi:10.3390/oxygen2010002

Abstract

Uterine transplantation may be a solution for infertility of uterine origin. Nevertheless, only three pregnancies with a live birth have so far been possible involving a uterine transplant from a brain-dead donor. Particularly, the impact of ischemia needs a better understanding. Analysis of mitochondrial respiration and production of reactive oxygen species (ROS) in muscle are of interest since they are pertinent markers of the harmful effects of ischemia. We therefore studied both uterine fundus and horn muscle mitochondrial use of oxygen and ROS production in eight women needing hysterectomy. High resolution respirometry and electron paramagnetic resonance allowed the determination of, respectively, myometrium oxidative capacity, hydrogen peroxide, mitochondrial free radical leak and superoxide anion production early (2 and 7 h) and late (24 h) following surgery. Mitochondrial oxygen consumption of the uterine fundus and horn tended to decrease with time but this was not statistically significant. Concerning ROS production, globally, we observed no significant change for H2O2, superoxide anion and free radical leak. In conclusion, a long period of cold ischemia did not impair myometrium mitochondrial respiration, only generating a transient H2O2 increase in uterine fundus. These data support that cold ischemia, even when prolonged, does not significantly alter uterine muscle oxidative capacity.

Highlights

IntroductionAlmost 200 women of reproductive age per million are suffering from uterine infertility that need uterine transplantation to allow pregnancy [1]
Almost 200 women of reproductive age per million are suffering from uterine infertility that need uterine transplantation to allow pregnancy [1].Proposed in cases of absent or dys-functionning uterus, uterus transplantation is still relatively rare
Little is known about the fate of mitochondria in the human uterus during transplantation and the purpose of this study was to determine the kinetics of mitochondrial respiration and of reactive oxygen species (ROS) production (2, 7 and 24 h after surgery) in two different segments of uterine myometrium subjected to cold ischemia as potentially observed during the clinical setting

Summary

Introduction

Almost 200 women of reproductive age per million are suffering from uterine infertility that need uterine transplantation to allow pregnancy [1]. Proposed in cases of absent or dys-functionning uterus (agenesia, hysterectomy, diverse malformations, Asherman syndrome, or endometriosis), uterus transplantation is still relatively rare. About 24 healthy children are born after uterine transplantation, resulting from over than 70 attempts worldwide. Brain-dead donors have only given rise to three live birth [2–20]. This clearly raises the issue uterine viability when subjected to long-lasting ischemia

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Discussion

Conclusion