IDENTIFICATION/CHARACTERIZATION OF NOVEL MATERNAL-EFFECT GENE PRODUCTS

点击翻译按钮获取中文摘要

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. The mammalian oocyte is a highly differentiated cell and contains a unique set of proteins necessary for directing its own fate to a fertilizable egg and producing a healthy embryo. We identified a group of six NLRP (NLR family, pyrin domain containing) genes that are specifically expressed in the oocyte in rhesus macaques; during preimplantation embryogenesis, these NLRPs are exclusively derived from the maternal (mother's) genome and decay rapidly upon embryo genome activation. Except for mouse NLRP5 that is required for embryogenesis beyond the 2-cell stage, functions of other NLRP family members are not known. Our preliminary data from nonhuman primates, along with recent findings in rodents and domestic animals, suggest that these oocyte-specific NLRP genes play important roles at multiple stages during oogenesis and early embryo development. The purpose of this project is to reveal the functions of selected oocyte-specific NLRPs in mice and rhesus macaques. The specific aims are to: (1) characterize in vivo functions of mouse NLRP4A, 4F and 14 using knockout mouse models; (2) demonstrate the in vitro postovulatory roles of selected NLRP genes (mouse Nlrp4a, 4f and 14; macaque NLRP4, 5 and 14) in mouse and macaque oocytes; (3) identify and analyze ovarian factors that interact with selected NLRP proteins in macaques. Due to the close resemblance in reproductive physiology and genetics between rhesus macaques and humans, the findings derived from this project will be easily extrapolated to human reproduction, and provide a basis for future translational research.