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

Separation of chromosomes in meiosis is a well-guarded process such that errors in chromosome segregation are rare events. For instance, only 1 in every 100000 divisions in yeast is associated with non-disjunction. Aneuploidy in germ cells of mammals like the mouse is generally much higher, in the range 0.5–1% [1]. Furthermore, there is a gender-specific difference in susceptibility to meiotic errors during germ cell formation in mammals, particularly in humans. On average, only 1–4% of sperm in healthy men have numerical chromosomal aberrations, while on average about 20% of all human meiosis II oocytes are aneuploid [1–4]. The correlation between the incidence of the birth of a trisomic child with Down's syndrome and maternal age was first recognized in 1933 by Penrose [5], confirmed by chromosomal analysis of spontaneous abortions and live births and, since the introduction of assisted reproduction, by evidence from polar bodies, oocytes, and embryos (e.g., [3, 6–8]). However, the cause(s) of the extraordinary susceptibility of aging oocytes to meiotic errors was obscure until recently.

Meiotic stages at which errors may occur

In typical mitosis there is division of sister chromatids derived from replication of each chromosome, and each pair therefore carries the same alleles along their arms (Figure 28.1A). In contrast, in meiosis I the two originally paternally and maternally derived homologs, each containing two sister chromatids, separate during first meiotic division (termed reductional division, Figure 28.1B, Ciii). They are normally physically attached to each other by at least one chiasma from recombination between sister chromatids of parental homologs (indicated by X in Figure 28.1B, Ci, Ciii). Chiasmata are held in place by cohesion between sister chromatid arms and centromeres (Figure 28.1Ci–Ciii) placed on chromatids before S-phase (Figure 28.1Ci), which is maintained until anaphase I (Figure 28.1Ciii, B) (reviewed in [9]). The paternal and maternal alleles along chromatid arms of recombined chromosomes switch left and right of a chiasma or exchange (indicated by different coloring in Figure 28.1B, Ci, E–J). Hence, the distribution of polymorphisms can be used to trace the origin and recombinational history of a chromosome in a zygote or child.

Wolbachia are gram-negative, intracellular bacteria that shelter in the gonads of invertebrates, and have profound effects on the fertility of their hosts. In some species, infected hosts can only reproduce parthenogenetically, in others cytoplasmic incompatibility prevents infected males from breeding with uninfected females, and in some cases genetically determined male embryos are transformed into females. Wolbachia engineers effects, as do all parasites, for selfish ends. Although this bizarre pathology is unknown in medical science, the relationships between microbes and human fertility are nonetheless complex, fascinating and important for the practice of reproductive medicine.

Unfortunately, and usually without advance warning, microbes occasionally enter the clinical laboratory through infected semen or vaginal tissue. When this occurs, a patient's treatment outcome may be seriously compromised because microbes can quickly deplete nutrients in culture media and alter the pH, and it would be irresponsible to knowingly transfer an infected embryo or semen to a patient. Bacterial and fungal growth are often obvious and easily tested, but how often do infectious agents go unrecognized and contribute to the problems of infertility, treatment failure and even possibly affect the child-to-be?

This is the first book on medical microbiology that has been written by experts in reproduction for clinical scientists and physicians in their own field. They are to be congratulated on filling a gap in the literature between microbiology and assisted reproduction, which they achieve in three sections.