Chromosomal instability in rhesus macaque preimplantation embryos

Abstract

Objective-To establish a relevant animal model to systematically investigate chromosomal instability in human oocytes and preimplantation embryos. Design-Prospective rhesus monkey IVF study.Setting-Academic laboratory, Oregon National Primate Research Center and Caribbean Primate Research Center. Patients-Young Rhesus macaque females.Interventions-In vitro produced (IVP) entire rhesus macaque preimplantation embryos were cytogenetically assessed using a 5-color fluorescent in situ hybridization (FISH) assay developed for rhesus macaque chromosomes homologous to human chromosomes 13, 16, 18, X and Y, using human bacterial artificial chromosome (BAC) probes.Main Outcome Measure(s)-Chromosomal abnormality rates in preimplantation embryos from young rhesus macaque females were established.Result(s)-Fifty preimplantation embryos, displaying good morphology and normal development, from 11 young rhesus macaque females were analyzed. Overall, 27 embryos (54%) were normal, 11 embryos (22%) mosaic, 3 embryos (6%) chaotic, 2 embryos (4%) aneuploid, 3 embryos (6%) haploid and 4 embryos (8%) triploid. Conclusion(s)-These data indicate that IVP rhesus macaque and human preimplantation embryos exhibit similar numerical chromosomal aberrations. Rhesus macaques appear to be a suitable animal model for investigating the origin of chromosomal instability observed in human preimplantation embryos.

Pluripotency genes overexpressed in primate embryonic stem cells are localized on homologues of human chromosomes 16, 17, 19, and X

“…Rhesus chromosomes 6 and 12 were shown to be under expressed in our experiments (Figure 3B). These results are in agreement with previous published results showing chromosomal instability in rhesus preimplantation embryos [36, 37]. When global gene expression patterns were characterized, we found that the nhpESC gene expression was closer to skin fibroblasts rather than to the teratoma fibroblasts, although genetically they share their genome with teratoma fibroblasts and only half with skin fibroblasts.…”

Inner Cell Mass Localization of NANOG Precedes OCT3/4 in Rhesus Monkey Blastocysts

“…Ovarian stimulation was carried out as previously described [26]. In brief, rhesus macaques received a sequential regimen of recombinant human gonadotropins to support follicular growth.…”

Incidence of chromosomal mosaicism in morphologically normal nonhuman primate preimplantation embryos

“…Ovarian follicular growth in female rhesus macaques (age range between 4 and 13 years old) was supported using sequential administrations of recombinant human follicle stimulating hormone (rhFSH, Organon, Oss, The Netherlands) and recombinant human luteinizing hormone (rhLH, EMD Serono, Rockland, MA, USA) (18, 19). On the final day of the rhFSH administration, a single dose of recombinant human chorionic gonadotropin (rhCG; 750–1000 IU, i.m.)…”

“…The procedures for oocyte recovery, sperm collection, insemination and embryo culture have been described previously (18–25). Fluid from ovarian follicles was aspirated 33 to 36 hours after the rhCG administration.…”

“…Since rhesus macaque and human IVP preimplantation embryos are comparable in vulnerability to chromosomal anomalies (18), the rhesus macaque is a good model to address this issue. In this retrospective study, cytogenetic data from previously analyzed morphologically normal day 3 rhesus macaque embryos (18, 19), which had at least 70% of their blastomeres analyzed, were used to provide insights into the mechanistic origins of mosaicism and implications for PGD and human infertility treatment in general.…”