Experimental ovarian tissue grafting : from ischemia to revascularization
(2010)
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- (en) Recent advances in cancer therapy have resulted in an increased number of long-term cancer survivors. Unfortunately, aggressive chemotherapy, ionizing treatment and bone marrow transplantation can severely affect the ovarian follicular reserve and subsequently lead to a loss of fertility and premature menopause. Ovarian tissue cryopreservation prior to gonadotoxic treatment, with the aim of reimplanting the frozen–thawed tissue once the patient has recovered, is an emerging technique to restore endocrine and reproductive function. Since ovarian tissue grafting is an avascular procedure, implants are exposed to ischemic damage during the post-transplantation period until they become revascularized. The aim of our study was to gain a better spatial and temporal understanding of ischemic and angiogenic processes from in vivo models of human ovarian tissue grafting. A better understanding of these processes is essential to find a way of protecting ovarian tissue from post-transplantation ischemic damage. In the first part of our study, we investigated the oxygen microenvironment of human ovarian xenotransplants in the early post-grafting period (until day 21) by means of EPR oximetry. This technique, which allows sensitive, non-invasive and repeated measurement of pO2 in vivo, was set up and validated to our mouce model. The critical early period of hypoxia was identified, its extent was quantified, and essential information was gathered on the first steps of reoxygenation following avascular human ovarian fragment transplantation. Our second objective was to investigate the revascularization process in human ovarian tissue in the same model of xenotransplantation. Both functional and morphological aspects of the vascular system were evaluated spatially and temporally by means of perfusion study combined with immunofluorescent staining of murine and human vasculature. This combined approach allowed us to determine the respective contribution of host and graft vessels to graft revascularization. Host and graft angiogenesis were found to contribute sequentially to ovarian tissue revascularization. We also characterized the angiogenic process leading to vascularization of human ovarian xenografts. Our findings suggest that the mechanism of ovarian graft revascularization results in an inosculation process (vascular link-up between graft and host vessels evidenced by chimeric vessels) and remodeling of pre-existent graft vessels. We propose a working hypothesis on the revascularization process in human ovarian xenotransplants. This hypothesis is the first step to understanding the revascularization process after human ovarian tissue xenografting. Questions still remain unanswered and need to be explored further.
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Van Eyck, A.-S. (2010). Experimental ovarian tissue grafting : from ischemia to revascularization. https://hdl.handle.net/2078.5/130778