Interphase Cytogenetics at the Earliest Stages of Human Development

Abstract

The widespread use of in vitro fertilization (IVF) throughout the world provides the opportunity to study human development at the very earliest stages before implantation. Nonetheless, the study of human embryos poses a series of unique ethical and moral implications. The unique totipotent nature of a human embryo and its potential to develop into a child necessitates a level of restriction and regulatory control that is not present when studying other cell types. Although some governments outlaw any experimental procedure on human embryonic material, others allow it under appropriate control. In the latter case (e.g., in the UK), experimentation can be justified on the basis of development of a diagnostic test and/or the goal of improving patient care. A further challenge to effective study is the paucity of material available. Much of the work reported in this chapter arises from the study of only single nuclei. For these reasons, research on interphase cytogenetics in human preimplantation embryos is less advanced than in other cell types. Despite this, a fundamental insight into chromosome copy number and nuclear organization can be gleaned from this material through collaboration with an appropriate clinical program. As attested by other chapters in this book, fluorescent in situ hybridization (FISH) was first adopted for research, but clinical applications rapidly followed. Prenatal and cancer diagnostics are the best examples of this,, but the increasing use of assisted reproductive technologies, namely IVF, precipitated the use of FISH in the field of preimplantation genetic diagnosis (PGD). PGD is defined as the diagnosis of genetic disorders in human preimplantation embryos. The purpose is selective implantation of unaffected embryos in the hope of establishing genetically normal ongoing pregnancies. PGD by interphase cytogenetics was first applied for sexing (to screen for sex-linked disorders), then for chromosome translocations, and later for chromosome copy number. In the latter case, termed preimplantation genetic screening (PGS), families at risk of adverse obstetrical outcomes (referral categories include advanced maternal age and recurrent miscarriage) are targeted, rather than families at risk of transmitting inherited disorders in a classical Mendelian fashion. Clinical application of interphase cytogenetics in the IVF world has allowed the subsequent study of chromosome copy number and nuclear organization. This chapter provides an overview of interphase cytogenetics in human embryos, highlighting the progress and the sometimes contentious pitfalls that it has encountered.