title: Primordial Follicle Transplantation within Designer Biomaterial Grafts Produce Live Births in a Mouse Infertility Model.
abstract: The gonadotoxic effects of chemotherapy and radiation may result in premature ovarian failure in premenopausal oncology patients. Although autotransplantation of ovarian tissue has led to successful live births, reintroduction of latent malignant cells inducing relapse is a significant concern. In this report, we investigated the design of biomaterial grafts for transplantation of isolated ovarian follicles as a means to preserve fertility. Primordial and primary ovarian follicles from young female mice were extracted and encapsulated into biomaterials for subsequent transplantation into adult mice. Among the formulations tested, aggregated follicles encapsulated within fibrin had enhanced survival and integration with the host tissue following transplantation relative to the fibrin-alginate and fibrin-collagen composites. All mice transplanted with fibrin-encapsulated follicles resumed cycling, and live births were achieved only for follicles transplanted within VEGF-loaded fibrin beads. The extent to which these procedures reduce the presence of metastatic breast cancer cells among the isolated follicles was evaluated, with significantly reduced numbers of cancer cells present relative to intact ovaries. This ability to obtain live births by transplanting isolated primordial and primary follicles, while also reducing the risk of re-seeding disease relative to ovarian tissue transplantation, may ultimately provide a means to preserve fertility in premenopausal oncology patients.
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA.|Department of Obstetrics and Gynecology, Institute for Women's Health Research, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kniazeva
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: A N
authors.initials: AN
authors.lastname: Hardy
authors.affiliation: Department of Obstetrics and Gynecology and Reproductive Medicine, CHU de Nice, Archet 2 Hospital, Nice, France.
authors.forename: S A
authors.initials: SA
authors.lastname: Boukaidi
authors.affiliation: Department of Obstetrics and Gynecology, Institute for Women's Health Research, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Woodruff
authors.affiliation: Department of Obstetrics and Gynecology, Institute for Women's Health Research, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.|Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Jeruss
authors.affiliation: Department of Chemical and Biological Engineering, McCormick School of Engineering, Northwestern University, Evanston, IL 60208, USA.|Department of Obstetrics and Gynecology, Institute for Women's Health Research, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.|Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Shea
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000473:pathology / Q000628:therapy*; D050498:Live Birth; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control*; D006080:Ovarian Follicle / Q000637:transplantation*; D011247:Pregnancy; D016649:Primary Ovarian Insufficiency / Q000473:pathology / Q000628:therapy*; D019737:Transplants / Q000637:transplantation*
chemical_list: D001672:Biocompatible Materials