Incidence and mechanisms of chromosomal anomalies during early development of rhesus macaques

Catherine Dupont, Wayne State University

Abstract

Significant incidences of aneuploidy in spontaneous abortions and in vitro produced (IVP) preimplantation embryos have led to the general conclusion that cytogenetic instability during human early development is a major hurdle for conception. The wide-ranging variability of reported aneuploidy frequencies in IVP human preimplantation embryos, however, has raised concerns that ovarian hormonal stimulation protocols and in vitro culture conditions may have a major impact on chromosomal instability during human early development. The experimentation of various artificial reproduction procedures in a closely-related animal model could lead to the comprehension and anticipation of cytogenetic instability originating as a result of artificial reproduction. In order to examine whether rhesus macaques are as susceptible as humans to aneuploidy during early development, IVP rhesus macaque preimplantation embryos were cytogenetically assessed using a custom made 5-color fluorescent in situ hybridization assay developed for rhesus macaque chromosomes homologous to human chromosomes 13, 16, 18, X and Y. The similarity of the aneuploidy frequencies in human and rhesus macaque preimplantation embryos has provided evidence that the rhesus macaque is a useful model to study cytogenetic instability during in vitro conception in humans. Using this model, insights into the etiology of phenomena observed in human in vitro fertilization clinics have been provided. Indeed, the large frequency of chromosomally abnormal rhesus macaque embryos derived from oocytes that were immature at retrieval in the present investigations potentially explains the poor viability of human embryos resulting from oocytes that matured shortly after retrieval. Additionally, a retrospective analysis of all analyzed rhesus macaque embryos in which at least 70% of the blastomeres were successfully evaluated provided insights into misdiagnosis rates following preimplantation genetic screening as well as the nature of segregation defects. The relative quantification of cohesins, shugoshins and spindle assembly checkpoint genes in rhesus macaque oocytes maturing following retrieval versus those mature at retrieval has resulted in the identification of gene expression patterns associated with a differential susceptibility to aneuploidy. Overall, this research has emphasized the utility of the rhesus macaque as a model to study frequencies and mechanisms of cytogenetic instability during human early development following the implementation of artificial reproduction procedures.

Recommended Citation

Catherine Dupont, "Incidence and mechanisms of chromosomal anomalies during early development of rhesus macaques" (January 1, 2009). ETD Collection for Wayne State University. Paper AAI3349770.
http://digitalcommons.wayne.edu/dissertations/AAI3349770