This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is part of a Roadmap Consortium (U54 RR02437, T. Woodruff, PI) entitled """"""""The Oncofertility Consortium: Fertility Preservation for Women"""""""". This project's goal is to validate options in nonhuman primates for restoring fertility in female cancer survivors by preventing ovarian exposure to the gametotoxic effects of therapy (by removing and preserving biopsies) and returning ovarian tissue, gametes or embryos for fertility. Studies will be performed in monkeys to:
(Aim 1) Bioengineer a scaffold that supports the three-dimensional architecture of the follicle and permits coordinated development of the follicle wall and oocyte in vitro;
(Aim 2) Evaluate the role of hormones and growth factors in promoting follicle growth and oocyte quality during culture;
(Aim 3) Optimize conditions for autotransplantation of ovarian cortex for coordinated follicle growth and oocyte maturation in vivo;
and (Aim 4) Assess fertilization and embryonic potential of oocytes derived from in vitro matured follicles and transplanted ovarian cortical follicles in vivo. Immature follicles will be isolated from macaque ovaries and cultured in an alginate matrix. Ovarian cortex will be autotransplanted to accessible sites (abdomen and forearm), and the ability of pro-angiogenic factors to restore ovarian function will be monitored. Mature oocytes produced by follicles in vitro and cortical transplants in vivo will be evaluated for reproductive potential by in vitro fertilization, embryo transfer into surrogate macaque mothers, pregnancy and health of offspring. This project is facilitated by interactions with the Biomaterials Core at Northwestern University. Expected advances will be transferred to clinical efforts at the Fertility Centers.
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