Long-term outcome of the fetal adrenal gland transplantation in rats

Abstract

Three experimental groups have been constructed to evaluate the long-term outcome of fetal adrenal transplantation in rats. In Group 1 (n = 10), rats underwent bilateral adrenalectomy. In Group 2 (n = 10), rats underwent a sham procedure which included flank incision and arterial canulization. In Group 3 (n = 20), a left adrenalectomy was performed followed immediately by transplantation of a fetal adrenal graft into the greater omentum and marked with a prolene suture (Stage 1). One year later, the right adrenal gland of the recipient was removed followed by a determination of the fetal adrenal graft function (Stage 2). Craft function was evaluated by measuring ACTH and corticosterone levels; and a histologic examination of the transplanted fetal adrenal gland was obtained at autopsy. In Group 1, all the rats died within first 8 hours, following bilateral adrenalectomy. In Group 2, and Group 3, all rats survived after Stage 1 operation. During the Stage 2 operation, it was observed that three rats (15 %) had neither fetal adrenal transplant nor prolene suture, seven rats (35 %) had a well vascularized and developed fetal adrenal graft and a prolene suture. There was no visible fetal adrenal graft but the prolene suture was present in the remaining rats (50 %) in Group 3. After removal of the right adrenal gland (6 and 12 hours later), the mean plasma level of ACTH increased with a decline in mean serum corticosterone level in Group 3 compared to the sham-operated animals (p < 0.001). In spite of visible, and viable transplants, all rats died within 48 hours following Stage 2 operation. The mean weight of the fetal adrenal transplant showed a sixteen-fold increase compared to the initial weight (p < 0.001) and histologic examination showed all 3 zones of adrenal cortex, but there were no medullary cells noted. Although the transplanted fetal adrenal grafts survived, their hormonal function was not enough to maintain host viability. Based on these results it is concluded that, insufficiency of the transplanted fetal adrenal gland may be secondary to either graft rejection or suppression of the transplanted tissue by the functional recipient adrenal despite the fetal adrenal transplant survival.