Both host and graft vessels contribute to revascularization of xenografted human ovarian tissue in a murine model

Abstract

Objective: To characterize the human ovarian xenograft revascularization process.

Design: Prospective experimental study.

Setting: Gynecology research unit in a university hospital.

Patient(s): Ovarian biopsies were obtained from 12 women aged 22-35 years.

Intervention(s): Frozen-thawed human ovarian fragments were intraperitoneally grafted into nude mice.

Main outcome measure(s): Graft perfusion was evaluated by Hoechst 33342 uptake. Murine and human vascularization was analyzed by CD31 and von Willebrand factor double immunostaining.

Result(s): On day 3, some murine neovessels and perfused areas were located at the periphery of the fragments. Nonperfused native human vessels were present in the fragments. From day 5, perfused areas and murine endothelial areas progressively increased. Host angiogenesis initiated ovarian graft reperfusion: murine neovessels penetrated from the periphery and were colocalized with perfused areas. By day 10, the increase in perfusion and murine vascularization was significant. The center of the fragments was perfused and a significant increase was observed in human vasculature.

Conclusion(s): Host and graft vessels contributed sequentially to graft revascularization: murine angiogenesis initiated reperfusion from day 5 and, by day 10, human angiogenesis was shown to participate in graft revascularization. Host and graft angiogenesis are potential targets to reduce the avascular period after grafting.