CHARACTERIZATION OF ZYGOTE ARREST ONE (ZAR1) IN NONHUMAN PRIMATES

Oregon Health & Science University, Portland OR

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Zygote Arrest One (ZAR1) is a key oocyte factor required for early embryogenesis in mice. Zar1 null female mice are infertile due to a developmental arrest at the zygote stage despite fairly normal folliculogenesis and ovulation. Little is known about the mechanism underlying ZAR1's functions as well as the roles of ZAR1 in species other than mice. We identified a ZAR1 ortholog in rhesus monkeys. Similar to the mouse Zar1 gene, monkey ZAR1 is preferentially expressed in the oocyte and early preimplantation embryos. I hypothesize that ZAR1 is required for complete fertilization and the embryonic genome activation in both mice and rhesus macaques. Applying in vitro mRNA injection and RNAi in the oocyte/zygote from both species, I propose to: (1) rescue the developmental arrest phenotype in periovulatory oocytes and zygotes derived from Zar1 null mice. The goal of the aim is to determine the critical timing when ZAR1 is required, and to observe the progress of each developmental stage and dynamic translocalization of ZAR1 during the oocyte-to-embryo transition by time-lapse live cell microscopy;and (2), deplete macaque ZAR1 in fully-grown and mature oocytes to demonstrate the role of ZAR1 in preimplantation embryo development. The goal of the aim is to elucidate whether ZAR1 is functionally conserved in primates. Data obtained from this project will allow us to apply for R01 funds for future in-depth mechanistic studies on ZAR1 and translational research in oocyte quality assessment and infertility therapies in women.