The application of Assisted Reproductive Technology (ART) to treat human infertility is still inefficient, when assessed on a per-embryo transferred basis. This is partly due to a high frequency of aneuploidy and mosaicism in embryos produced by in vitro fertilization, which reduces or prevents their viability. The reason(s) for these high error rates is not fully understood, but meiotic non-disjunction appears to be a major source of oocyte and embryo chromosome anomalies. Several factors in the infertile women patients and their clinical treatment may predispose to high chromosome error frequencies but it is very difficult to discriminate among these sources in humans. A suitable animal model is needed for experimental studies on the etiology of these errors. Macaque monkeys are ideal for this purpose because of their close similarities to humans. In this pilot study, we plan to determine the aneuploidy (non-disjunction) frequency in oocytes and the mosaicism frequency in embryos derived from these oocytes, to provide baseline data for supporting larger, more detailed studies. Oocytes obtained from necropsied macaque ovaries will be matured in vitro, then (i) analyzed by fluorescent in situ hybridization with human chromosome probes or by karyotyping, and (ii) fertilized in vitro to make cleavage stage embryos that will be similarly analyzed for mosaicism We will develop these probes to work with macaque chromosomes, which will facilitate this and future studies. This study will establish a macaque model for studies on the etiology of aneuploidy and mosaicism in human embryos. The information to be derived can be used to modify current ART protocols to reduce the frequency of artificially induced chromosome errors in embryos produced in vitro.
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