In vitro Development of Ovarian Follicles

Evelyn E. Telfer, Ph.D.; Marie McLaughlin, Ph.D.

Disclosures

Semin Reprod Med. 2011;29(1):15-23. 

In This Article

Abstract and Introduction

Abstract

Tissue banking of ovarian material is being increasingly offered to a variety of patients as a means of fertility preservation. This tissue comprises thin cortical surface biopsies that contain predominantly primordial follicles, and currently the only option to restore fertility is by transplantation. However, this is not a viable option for all patients. The potential of this tissue could be realized by the development of in vitro systems to support complete growth from the early primordial stages through to maturity. This technology would have many therapeutic applications including the production of competent oocytes for assisted reproduction technologies, determination of toxicological effects on germ cell development, assessment of cryopreserved ovarian tissue before transplantation for fertility preservation as well as providing an experimental model to address basic scientific questions concerning human oocyte development. Complete oocyte development in vitro from the primordial stage has been achieved in mice, but the larger size and longer growth period of human follicles has made the interspecies translation of these techniques difficult. Recently progress has been made in defining conditions that support different stages of follicle development in vitro that make a complete in vitro system from primordial to maturation a possible reality. This article deals with our current understanding of in vitro development.

Introduction

In humans the female germ cell population is formed before birth. It is accepted that it is not substantially replenished during adult life[1] and that the fate of almost all of these germ cells is death.[2–4] At any age the human ovarian follicle reserve is composed of primordial follicles, a pool that is continually depleted during reproductive life.[5,6] The relative abundance and lack of differentiation of primordial follicles makes this population an ideal choice for in vitro growth to obtain fertilizable oocytes for potential use in advanced reproductive technologies (ART) and fertility preservation programs.[7,8] The ability to develop these immature follicles fully in vitro would facilitate greater understanding of the mechanisms regulating oocyte development as well as providing a model system to determine the effect of chemotherapeutic agents on oocyte development.

The capacity of immature mammalian oocytes to develop fully in vitro has already been demonstrated in rodents with the birth of pups from in vitro matured oocytes derived from murine cumulus-oocyte complexes,[9] primordial follicles,[10,11] and cultured primary follicles.[12] However this has yet to be successfully repeated using incompetent oocytes from human follicles that undergo a protracted developmental period in vivo. Although definition of a complete in vitro system has yet to be achieved, a great deal of basic scientific progress has been made using systems designed to support the partial growth of human follicles. The several developmental milestones accomplished include follicle activation,[13–18] preantral follicle growth,[13,15,17,19–23] follicle differentiation,[13,21] and oocyte maturation[24,25] using fresh and cryopreserved human tissue. In the clinical setting, progress has been made with the ability to apply in vitro maturation (IVM) techniques to immature human oocytes with subsequent in vitro fertilization (IVF) of these oocytes leading to pregnancy and live births.[26–28] Despite the successes, stumbling blocks still exist, notably oocyte degeneration associated with the disruption of the contact between the oocyte and its companion somatic cells over time. Therefore it is vital that we gain a better understanding of how culture conditions impact on the maintenance of appropriate cell interactions during follicle development.

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