A bioengineered in situ ovary (ISO) supports follicle engraftment and live-births post-chemotherapy

Author:

Buckenmeyer,Michael [ORCID]

Sukhwani, Meena

Iftikhar, Aimon

Nolfi, Alexis L

Xian, Ziyu

Dadi, Srujan

Case, Zachary W

Steimer, Sarah R

D'Amore, Antonio

Orwig, Kyle E

Brown, Bryan N
Author Address

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA., McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA., Department of Obstetrics, Gynecology and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Fondazione RiMED, Palermo, Italy.,

Abstract:

Female cancer patients who have undergone chemotherapy have an elevated risk of developing ovarian dysfunction and failure. Experimental approaches to treat iatrogenic infertility are evolving rapidly; however, challenges and risks remain that hinder clinical translation. Biomaterials have improved in vitro follicle maturation and in vivo transplantation in mice, but there has only been marginal success for early-stage human follicles. Here, we developed methods to obtain an ovarian-specific extracellular matrix hydrogel to facilitate follicle delivery and establish an in situ ovary (ISO), which offers a permissive environment to enhance follicle survival. We demonstrate sustainable follicle engraftment, natural pregnancy, and the birth of healthy pups after intraovarian microinjection of isolated exogenous follicles into chemotherapy-treated (CTx) mice. Our results confirm that hydrogel-based follicle microinjection could offer a minimally invasive delivery platform to enhance follicle integration for patients post-chemotherapy. © The Author(s) 2023.

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