Developmental Status: Impact of Short-Term Ischemia on Follicular Survival of Whole Ovarian Transplantation in a Rabbit Model

Abstract

Ischemia is the first mechanism that provokes the loss of follicles in ovarian grafts over the long term. In whole ovarian transplantation, it remains unknown, however, how changes in follicular development are influenced by short-term ischemia. Fresh whole ovarian orthotopic auto-transplantation was performed in rabbits with 45 min ischemia, and the impact of ischemia on follicular survival and development status was evaluated at different time-points (1 day, 3 days, 1 week, 2 weeks and 1 month). Assessment of follicular quantity and morphology was carried out via histologic analysis. Follicle proliferating status was evidenced by immunostaining with proliferating cell nuclear antigen (PCNA), and the Hedgehog signaling pathway (Patched and Gli); was verified via TUNEL assay. Quantitative PCR was carried out to quantify the mRNA of target genes including PCNA, Patched, Gli, Caspase 3, Bax, and Bcl-2. Compared with its contralateral fresh controls, the morphology, proliferation and apoptosis of the follicles in the grafts showed no significant differences and most primordial follicles were quiescent. However, morphology and proliferation status were significantly decreased 1 week after grafting, in comparison with the longitudinal grafting time. Patched and Gli in the Hedgehog signaling pathway were activated in only the follicles of the grafts. Short-term ischemia slightly impacts follicular survival and development status in whole ovarian grafting. Receiving intervention in the first week post-transplantation might be helpful.

Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice

“…Simultaneously, during the same period, increase of the number and volume of tertiary follicles showed follicular growth continued and was enhanced after heterotopic transplantation. Consistent with our findings, Xie et al [ 3 ] recently showed that healthy rate of follicles and the number of follicles with positive proliferating cell nuclear antigen in primary follicles decreased 1 month after orthotopic autografting of the rabbit ovaries. Early follicular development is regulated by ovarian autocrine/paracrine regulators and interactions between oocyte-granulosa cells, ovarian stromal cells, and theca cells affect this process [ 14 ].…”

“…On the other hand, ovarian transplantation has the potential application for maintaining the fertility after chemotherapy and radiotherapy in women [ 2 ]. As a result of the ovarian transplantation, the possible depletion of follicle reserve and limitation of fertility restoration exist [ 3 ]. The major concern in grafting is that the graft survival is completely dependent on the establishment of neovascularization [ 4 ].…”

Whole Ovary Cryopreservation and Transplantation: A Systematic Review of Challenges and Research Developments in Animal Experiments and Humans

“…Vascular transplantation of fresh whole ovaries has been largely successful in animal models (rats [ 103 , 104 , 105 ], rabbits [ 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ], sheep [ 47 , 49 , 67 , 68 , 78 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ], pigs [ 122 , 123 ], dogs [ 124 ] and monkeys [ 125 , 126 ]). Encouraging results have also been reported on transplantation of frozen–thawed whole ovaries in rats [ 66 , 127 , 128 , 129 ], rabbits [ 130 ] and sheep [ 38 , 40 , 41 , 48 , 49 , 50 , 67 , 68 , 78 , 95 , 102 , 131 ], which will be detailed further in this review.…”

Follicular development and the expression of BAX and vascular endothelial growth factor in transplanted ovaries in uni- and bilateral ovariectomized mice: An experimental study

“…Ischemia and degeneration of follicles are important factors, which should be considered during the transplantation of ovarian tissue and it can cause a decline in ovarian reserve and fertility potential (5)(6)(7)(8). The vascular condition of the graft site plays a critical role in the reduction of ischemia.…”

“…The vascular condition of the graft site plays a critical role in the reduction of ischemia. Therefore, angiogenesis in transplanted tissue and growth of the ovarian follicles depends on the graft site (5,6,8). Vascular endothelial growth factor (VEGF) plays an important role in the posttransplantation angiogenesis of ovarian tissue (9)(10)(11).…”