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.

Ovarian regeneration: The potential for stem cell contribution in the postnatal ovary to sustained endocrine function

“…granulosa and oocytes, with or without theca cells) creates an ‘artificial’ ovarian environment which supports human oocyte maturation (Krotz et al, 2010). Similar approaches have been reported using cells and tissues from mice, rats, non-human primates and humans (Xu et al, 2006; Laronda et al, 2014; Hornick et al, 2012; Xu et al, 2009; Luyckx et al 2013, 2014; Díaz-García and Herraiz, 2014, Liu et al, 2013, 2014; Kniazeva et al, 2015), albeit with the goal of follicle maturation rather than endocrine function. The potential utility in restoration of endocrine function has only recently been explored.…”

A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice

“…These results are very encouraging and have validated both the model procedure and the need for graft vascularization for complete restorative organ function of isolated follicles in a biomaterial1819. However, hydrogel encapsulation of follicles poses several challenges, especially with respect to the size of anticipated transplants.…”

Where are Oncofertility and Fertility Preservation Treatments Heading in 2016?

“…Another interesting way is to transplant primordial follicles within artificial biomaterial grafts. A recent paper reported the successful production of offspring in mouse infertile model following transplantation of primordial follicles within artificial biomaterial grafts [54]. Several investigators are studying whether deleterious epigenetic events occur in cultured follicles [55,56].…”