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Vascular Remodeling and Angiogenesis in Ectopic Ovarian Transplants: A Crucial Role of Pericytes and Vascular Smooth Muscle Cells in Maintenance of Ovarian Grafts¹

Department of Biological Regulation, The Weizmann Institute of Science, Rehovot 76100, Israel

Cancer patients, treated by either chemo- or radiotherapy, frequently suffer from ovarian failure and infertility. One of the new emerging techniques to preserve reproductive potential of such patients is cryopreservation of ovarian fragments prior to treatment and their retransplantation after healing. A major obstacle in survival of the ovarian implants is vascular failure, which leads to tissue necrosis. In order to investigate the role of angiogenesis in implant preservation, we used a xenograft model in which rat ovaries were transplanted into immunodeficient mice. Graft reception and maintenance were monitored by magnetic resonance imaging (MRI) and histology. Two transplantation sites were explored, i.e., subcutaneous and intramuscular. Comparison between these two transplantation sites revealed the importance of vascular smooth muscle cells and pericytes in sustaining vascular and tissue integrity. Histological examination of the grafts, at different time points and sizes, revealed that loss of perivascular cells preceded damage to endothelial cells and was closely correlated with loss of follicular and oocyte integrity. Intramuscular implantation provided better maintenance of implant perivascular cells relative to subcutaneous implantation. Accordingly, follicular integrity was superior in the intramuscular implants and the number of damaged follicles was significantly lower compared with the subcutaneous transplantation site. These results suggest that improving ovarian implant maintenance should be directed toward preservation of perivascular support.

¹ This work was supported by a research grant from the U.S. National Cancer Institute RO1 CA75334 (M.N.) and The Maria and Bernhard Zondek Hormone Research Fund (A.T.). A.T. is the incumbent of the Hermann and Lilly Schilling Foundation Professorship.

² Correspondence. FAX: 972 8 9342487; michal.neeman{at}weizmann.ac.il

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