Primordial Follicle Transplantation within Designer Biomaterial Grafts Produce Live Births in a Mouse Infertility Model

E. Kniazeva, A. N. Hardy, S. A. Boukaidi, T. K. Woodruff, J. S. Jeruss*, L. D. Shea

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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.

Original languageEnglish (US)
Article number17709
JournalScientific reports
Volume5
DOIs
StatePublished - Dec 3 2015

Funding

The authors would like to thank Kenan Moss and Sayali Kale for their contribution in collecting in vitro follicle characterization data, as well as imaging and quantification of histology tissue. We also thank Dr. Eiji Saito for assistance in collection of vaginal lavage samples for breeding studies and Dr. Samira Azarin, Dr. Shreyas Rao and Brian Aguado for helping with acquisition of flow cytometry data from cancer-inoculated mice. Finally, we thank Dr. Ariella Shikanov, Dr. Min Xu, Rachel Mullin and Woodruff lab members for helpful discussions regarding data collection and processing. Funding for this research was provided by the National Institutes of Health, grant U54 HD076188.

ASJC Scopus subject areas

  • General

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