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

Abstract

The endocrine function of the ovary is dependent upon the ovarian follicle, which on a cellular basis consists of an oocyte surrounded by adjacent somatic cells responsible for generating sex steroid hormones and maintenance of hormonal stasis with the hypothalamic-pituitary axis. As females age, both fertility and the endocrine function of the ovary decline due to waning follicle numbers as well as aging-related cellular dysfunction. Although there is currently no cure for ovarian failure and endocrine disruption, recent advances in ovarian biology centered on ovarian stem cell and progenitor cell populations have brought the prospects of cell- or tissue-based therapeutic strategies closer to fruition. Herein, we review the relative contributions of ovarian stem cells to ovarian function during the reproductive lifespan, and postulate steps toward the development of ovarian stem cell-based approaches to advance fertility treatments, and also importantly to provide a physiological long-term means of endocrine support.

Keywords: Female germline stem cell; Granulosa cell; OSC; Ovary; Stem cells.

Copyright © 2016. Published by Elsevier B.V.

Figures

Fig. 1

Immunofluorescent micrographs of human ovarian tissue during development (56 days, 137 days) and from reproductive-age ovarian tissue reveals break down of the germ cell nests and formation of primordial follicles. At 56 days of development, PGCs/oogonia cluster in cords, segregated from somatic cells. Subsequently, germ cell nests begin to breakdown (shown here at 137 days of development) to create primordial follicles (white arrows in center image) consisting of an oocyte surrounded by several squamous pregranulosa cells. In the adult human ovary, primordial follicles persist as an oocyte surrounded by a single layer of pre-granulosa cells. Scale bar = 20 microns. Immunofluorescence staining for beta-catenin (pink) and counterstained with Hoechst to stain nuclei (blue). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Schematic summary of ovarian cell types and putative cell sources required for the production of an “artificial” ovary with the dual purpose of the generation of fertilization competent oocytes, as well as the capability of functional communication with the hypothalamic-pituitary axis. Pluripotent stem cell derived ovarian somatic cells (granulosa and/or theca) can be combined with OSCs or PGCLCs within a biomatrix to create the “prosthetic” ovary. Abbreviations: MSC - mesenchymal stem cells, SF-1 – steroidogenic factor 1, ESC – embryonic stem cell, OSC – oogonial stem cell, PGC – primordial germ cell, GnRH – gonadotropin releasing hormone, LH – luteinizing hormone, FSH - follicle stimulating hormone, HPG – hypothalamic-pituitary-gonadal.