Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations

Abstract

Pre-implantation embryo development in mammals begins at fertilization with the migration and fusion of the maternal and paternal pro-nuclei, followed by the degradation of inherited factors involved in germ cell specification and the activation of embryonic genes required for subsequent cell divisions, compaction, and blastulation. The majority of studies on early embryogenesis have been conducted in the mouse or non-mammalian species, often requiring extrapolation of the findings to human development. Given both conserved similarities and species-specific differences, however, even comparison between closely related mammalian species may be challenging as certain aspects, including susceptibility to chromosomal aberrations, varies considerably across mammals. Moreover, most human embryo studies are limited to patient samples obtained from in vitro fertilization (IVF) clinics and donated for research, which are generally of poorer quality and produced with germ cells that may be sub-optimal. Recent technical advances in genetic, epigenetic, chromosomal, and time-lapse imaging analyses of high quality whole human embryos have greatly improved our understanding of early human embryogenesis, particularly at the single embryo and cell level. This review summarizes the major characteristics of mammalian pre-implantation development from a chromosomal perspective, in addition to discussing the technological achievements that have recently been developed to obtain this data. We also discuss potential translation to clinical applications in reproductive medicine and conclude by examining the broader implications of these findings for the evolution of mammalian species and cancer pathology in somatic cells.

• Aneuploidy
• cancer
• chromothripsis
• embryo
• evolution
• fragmentation
• IVF
• micronuclei
• preimplantation

Acknowledgments

We gratefully acknowledge the National Centers for Translational Research in Reproduction and Infertility (NCTRI)/NICHD (P50 HD071836), Howard and Georgeanna Jones Foundation for Reproductive Medicine, Medical Research Foundation of Oregon, and the Collins Medical Trust to SLC for funding.

Declaration of interest

The authors report no conflicts of interest.

Author contributions

Conceived of review: SLC; Analyzed the data: LC, SLC; Wrote the manuscript: LC, SLC. Both authors approved the revisions and final manuscript.