title: Fibrin-mediated delivery of an ovarian follicle pool in a mouse model of infertility.
abstract: The cryopreservation and autotransplantation of ovarian tissue is emerging as a powerful approach for preserving fertility. However, for cancer patients, it may not be possible to transplant ovarian tissue due to the risk of re-seeding disease. We investigated strategies for transplantation of individually isolated follicles to minimize the risk of re-introducing cancer cells present within the vasculature of ovarian stroma. Procedures for large-scale isolation of early-stage follicles and their encapsulation into fibrin hydrogels were developed. For in vivo validation studies, mice were ovariectomized and transplanted with encapsulated follicles into the ovarian bursa. A substantial increase in the number of secondary follicles was observed in the graft at 9 days after transplantation, and antral follicles by day 21, demonstrating primordial follicle recruitment into the growing pool. Initially, elevated follicle-stimulating hormone levels declined substantially by day 21, indicating feedback from the graft; presence of corpora lutea showed the graft's capability of restoring hormone cyclicity. Taken together, the transplanted follicles were able to engraft, mature, and restore ovarian function in an infertile mouse. This biomaterial may, thus, provide a platform for follicle transplantation with a low risk of cancer contamination and for developing strategies that preserve fertility for women facing a cancer diagnosis.
authors.affiliation: 1 Department of Chemical and Biological Engineering, Northwestern University , Evanston, Illinois.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Smith
authors.forename: Ariella
authors.initials: A
authors.lastname: Shikanov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kniazeva
authors.forename: Deepa
authors.initials: D
authors.lastname: Ramadurai
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D005260:Female; D059247:Fertility Preservation / Q000379:methods*; D005340:Fibrinogen / Q000737:chemistry*; D007247:Infertility, Female / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000637:transplantation*; D009924:Organ Culture Techniques / Q000379:methods; D006080:Ovarian Follicle / Q000637:transplantation*; D010052:Ovariectomy; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D005340:Fibrinogen