Differential Scanning Calorimetry, a Novel Method to Detect Uterine Ischemia-Reperfusion Injury During Autotransplantation in Experimental Sheep Model.

Background/

Objectives

A novel treatment of absolute uterine factor infertility is uterus transplantation. In preparation for human surgery, autotransplantation was performed in a sheep model to assess ischemia-reperfusion injury of the uterine wall.

Methods

Seven multiparous ewes underwent live-donor uterus autotransplantation; in six, the procedure was completed successfully. Tissue blocks of complete uterine wall, endometrium, and myometrium were obtained at four predefined time points: native (baseline), after 1 h of cold ischemia, after 30 min of warm ischemia, and after 30 min of reperfusion. Samples were analyzed by differential scanning calorimetry and routine hematoxylin-eosin histology.

Results

Histology demonstrated preserved epithelial, glandular, and stromal structures, with only minimal, reversible changes that increased with the ischemic duration. Differential scanning calorimetry confirmed alterations in thermal stability: in the uterine wall and myometrium, the calorimetric enthalpy decreased from baseline (3.40 ± 0.53 J/g) to reperfusion (2.62 ± 0.22 J/g), indicating structural loosening; in contrast, the endometrium calorimetric enthalpy slightly increased, suggesting greater flexibility and less susceptibility to ischemia-reperfusion injury.

Conclusions

In this preliminary study, differential scanning calorimetry proved to be an effective and sensitive method for detecting early structural alterations in the uterine wall that could negatively impact post-transplant function. Cold and warm ischemia did not cause irreversible damage within a two-hour time frame, supporting the feasibility of short-term preservation in uterus transplantation. The myometrium demonstrated more significant vulnerability than the endometrium, which highlights the necessity of protective strategies to preserve smooth muscle integrity during transplantation.