Metabolic alterations of uterine grafts after extended cold ischemic storage: experimental study in ewes

Abstract

Uterine transplantation from a deceased donor could become an available option for widely treating uterine infertility. However, this procedure requires more precise knowledge about the graft's tolerance to extended cold ischemia. Here, we sought to assess the uterine metabolic alterations after extended cold ischemic storage in a model of auto-transplantation in ewe. A total of 14 uterine auto-transplantations were performed, divided into 2 groups: 7 after 3 h of cold ischemia time (CIT) and 7 after 24 h. Venous uterine blood was collected before uterus retrieval and during reperfusion (30, 60 and 90 min); thereafter, blood gases, lactate, glucose and amino acids (AAs) were analyzed. Apoptosis analyses were performed before uterus retrieval and following reperfusion in uterus biopsies. A total of 12 uterine auto-transplantations were successfully performed and 7 ewes were alive ≥8 days after transplantation. After reperfusion, a decrease in pH, a rise of lactate and lactate/glucose ratio and a delayed decrease of pO2 were found in the 3 h CIT group. No significant variation of these parameters was observed in the 24 h CIT group. Significant decreases of AAs were observed during reperfusion and these decreases were more pronounced and concerned a larger number of compounds in the 24 h CIT group than in the 3 h CIT group. There was no significant uterine apoptotic signal in either group. Overall, these results suggest that extended CIT storage delayed restoration of aerobic glycolysis and induced an increase in AA requirements of the uterus after reperfusion. However, this biochemical alteration did not reduce success rate for uterine transplantation.

Keywords: apoptosis; cold ischemic injuries; energy metabolism; ischemia/reperfusion injuries; uterus transplantation.