Antoine Tardieu1,2, P Chazelas3,4, P-A Faye3,4, F Favreau3,4, L Nadal-Desbarats5, C Sallée6, F Margueritte6, C-Y Couquet7, P Marquet8, C Barin-Le Guellec8,5, T Gauthier8,6. 1. INSERM, Inserm Unit U1248, 87000, Limoges, France. antoine.tardieu@hotmail.fr. 2. Department of Gynecologic and Obstetric, Hospital of Limoges, 87000, Limoges, France. antoine.tardieu@hotmail.fr. 3. Faculty of Medicine, EA 6309 "Maintenance Myélinique et Neuropathies Périphériques", University of Limoges, 87000, Limoges, France. 4. Laboratory of Biochemistry and Molecular genetics, Hospital of Limoges, 87000, Limoges, France. 5. Faculty of Medicine, University of Tours, 37000, Tours, France. 6. Department of Gynecologic and Obstetric, Hospital of Limoges, 87000, Limoges, France. 7. Platform of Medicine, Imagery and experimental surgery (MICE), Hospital of Limoges, 87000, Limoges, France. 8. INSERM, Inserm Unit U1248, 87000, Limoges, France.
Abstract
INTRODUCTION: The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes. METHODS: Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR). RESULTS: Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05). CONCLUSION: The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation.
INTRODUCTION: The development of uterine transplantation (UTx) from deceased donors requires knowledge of the tolerance of the uterus to prolonged cold ischemia (CI). This can be evaluated through the use of biological parameters to assess degradation of the organ between its procurement and transplantation. The objective of this study was to analyze changes in the metabolic composition of the storage solution in cases of prolonged CI in uteri from ewes. METHODS: Eighteen uterine auto-transplantations were performed in ewes. CI time was 1 h (T1) or 24 h (T24). Samples of Celsior® were taken when the explanted uterus was flushed (T0) and at the end of CI. A dual approach to metabolic analyses was followed: targeted biochemical analyses targeting several predefined metabolites and non-targeted metabolomics analyses based on nuclear magnetic resonance (NMR). RESULTS: Metabolic analyses were performed on 16 explanted uteri. Metabolomic profiles differed significantly between T1 and T24 (p = 0.003). Hypoxia-associated degradation of the organ was demonstrated by the significantly higher lactate levels at T24 than at T1 (p < 0.05), accompanied by cell lysis, and significantly higher levels of creatine kinase activity in T24 than in T1 uteri (p < 0.05). Oxidative stress increased over time, with a significantly higher oxidized glutathione/glutathione ratio for T24 than for T1 uteri (p < 0.05). CONCLUSION: The metabolic results indicate a significant degradation of the uterus during 24 h of CI. Metabolic analysis of the storage solution could be used as a non-invasive tool for evaluating uterine degradation during CI before transplantation.