Introduction

Oocyte cryopreservation is a major issue in human reproductive medicine. The need to cryopreserve oocytes rather than embryos is not limited to countries with restrictive legislation. In fact, all the major clinical applications rely on fertility preservation for both medical and non-medical reasons [1–4] and for oocyte donation programs [5–7].

The first success in freezing human oocytes was reported by Chen [8] using a slow-cooling method in dimethyl sulfoxide (DMSO) as the cryoprotectant. The technique was essentially a modification of that used for cryopreservation of human embryos, which in turn had evolved from methods applied for freezing mouse and cattle embryos. Out of 40 thawed oocytes, the reported survival, fertilization, and cleavage rates were 80%, 83%, and 60%, respectively. Despite the technique resulting in a twin pregnancy, its adoption in human reproductive medicine was delayed, due to the failure to reproduce the results reported. Concerns were expressed about the difficulty in dehydrating and cooling human oocytes due to their large volume, the sensitive nature of the metaphase nucleus, premature cortical granule release, and interruption to intercellular ultrastructure [9, 10].

When approached by Nick Dunton of Cambridge University Press to edit the second edition of The Biology and Pathology of the Oocyte, my response was an emphatic yes, providing my co-editor Roger Gosden could be enticed from retirement. He agreed and we both wanted Ursula Eichenlaub-Ritter to be the third editor because we admired her expertise in the basic biology of the oocyte and her ability to get the job done. There has been incredible progress in the knowledge of the oocyte and applications for medicine that have regularly appeared since the first edition. We considered the areas of reproductive technology – IVF – and the areas of reprogramming somatic cell phenotype as spin-offs of the progress made in oocyte biology. Both these areas received Nobel Prizes in the last few years and are included in the contributions for the second edition. We were fortunate to have John Gurdon open the second edition the year (2013) after he won the Nobel Prize in Physiology or Medicine. He and his coauthor set the scene for a rather different perspective of the power and influence of the oocyte in modern biology. The contributors invited for the second edition are exceptional in their areas of oocyte biology, pathology, and applications to biotechnology and medicine. We think they have captured the excitement of the fast-moving frontier of the oocyte field.

The second edition will enthuse the reader interested in how the oocyte is formed, its function, and the underlying mechanisms of what is the most extraordinary cell in the body. It remains the germinal link from generation to generation and must undergo the most elaborate series of changes to be ready to accept the genomic contribution of the most differentiated of all cells – the sperm. The oocyte must then enter the developmental program that enables an organism to arise with extremes in patterning and lineage differentiation consistent with the species of origin. In this exquisitely crafted program of development, it is possible to intervene to manipulate the oocyte for purposes of solving human infertility, to clone animals, develop pluripotent embryonic stem cells, and reprogram cell commitment in fully differentiated cells in animals including the human – so-called induced pluripotent stem cells (iPSCs). As a consequence we are able to address human infertility and avoid some of the worst inheritable genetic diseases, enable advances in selective animal breeding, and potentially address many human pathologies by using stem cell therapies.

Introduction

The oocyte and the follicle are, in the female mammal, intimately linked from the early phases of gam - etogenesis. They form a duo in which the death of one component normally induces the death of the other. During the passage from the primordial to the primary and the secondary stages, both compartments show a large number of synchronized changes indicating that, even at the earliest stage, they influence or depend on each other. Until the oocyte reaches its full size, it is quite clear that the follicular cells provide substrate, as well as complementary proteins necessary for oocyte function. The competence of the fully grown oocyte varies according to species. In the mouse, the ability to resume meiosis is reached around a diameter of 70 µm while the ability to be fertilized and normal development is only achieved when the oocyte reaches maximum size (First et al., 1988). In domestic animals, the acquisition of developmental competence is not necessarily achieved in full-size oocytes. It seems that other differentiation events relating to follicular development are required for the full developmental competence to be achieved.

In this chapter, the importance of different aspects of follicular development will be analysed for their influence on the ability of the oocyte to be aspirated, to mature in vitro and to develop as a normal embryo following fertilization. Since the dynamics of the interaction between the oocyte and the follicle compartment are similar in farm animals and humans, most of the examples are drawn from the cow and, when available, a comparison will be made with information available for other species.

In animals, a rationale for the apparent cross-talk between the oocyte and the follicle comes from the requirement for the ovulation of an oocyte at the right time since most animals do not mate at random during the sexual cycle. The reproductive behaviour in most animals limits the sexual interaction to the period immediately before or after ovulation to achieve a maximal rate of conception. The connection between the ovulatory process and reproductive behaviour is mainly linked to the absolute level of circulating oestradiol 17β which is produced mainly by a mature follicle containing a fully grown oocyte.