The overall goal of this application is to evaluate protocols important for the exploitation of ART that can enhance the propagation of NHP models of human disease. The use of ART to produce embryos from genetically valuable animals can contribute to a wide range of studies related to human health, from infertility to degenerative diseases. However, the current state of basic ART procedures in NHPs, such as embryo transfer and production of identical twins, is poor. Few studies have been devoted to improving these procedures. The proposed research will routinely produce embryos from rhesus monkeys using standard in vitro fertilization and embryo culture protocols in order to evaluate several different technical approaches to improve the production of animals for health related research.
The aims of this resource development application are to evaluate: 1) strategies (number and stage of embryos) for transferring embryos to recipient females, in order to improve the success rate in producing offspring; 2) cross-species embryo transfer in macaques, in order to facilitate intra-uterine transfers; 3) the effectiveness of simple methods of blastomere separation or embryo splitting to produce identical twins; 4) a procedure for producing multiple embryos in vivo by superovulation and uterine flushing, thus avoiding possible artifacts from culturing in vitro produced embryos; and 5) preimplantation genetic diagnosis as a tool for selecting macaque embryos with specific genetic characteristics prior to embryo transfer, as a means to increase the efficiency of ART for propagating genetically valuable animals. By combining several of these technologies, the investigators will enhance the efficacy and utility of NHPs for health-related research, increase the fecundity of genetically-valuable animals, and improve the ability to select for specific genetic characteristics when breeding NHPs.
|Dupont, Catherine; Harvey, Alexandra J; Armant, D Randall et al. (2012) Expression profiles of cohesins, shugoshins and spindle assembly checkpoint genes in rhesus macaque oocytes predict their susceptibility for aneuploidy during embryonic development. Cell Cycle 11:740-8|
|Harvey, Alexandra J; Mao, Shihong; Lalancette, Claudia et al. (2012) Transcriptional differences between rhesus embryonic stem cells generated from in vitro and in vivo derived embryos. PLoS One 7:e43239|
|Nichols, Stephanie; Harvey, Alexandra; Gierbolini, Lynette et al. (2010) Long-distance transportation of primate embryos developing in culture: a preliminary study. Reprod Biomed Online 20:365-70|
|Dupont, Cathérine; Segars, James; DeCherney, Alan et al. (2010) Incidence of chromosomal mosaicism in morphologically normal nonhuman primate preimplantation embryos. Fertil Steril 93:2545-50|
|Nichols, Stephanie M; Gierbolini, Lynette; Gonzalez-Martinez, Janis A et al. (2010) Effects of in vitro maturation and age on oocyte quality in the rhesus macaque Macaca mulatta. Fertil Steril 93:1591-600|
|Harvey, A J; Armant, D R; Bavister, B D et al. (2009) Inner cell mass localization of NANOG precedes OCT3/4 in rhesus monkey blastocysts. Stem Cells Dev 18:1451-8|
|Dupont, Cathérine; Froenicke, Lutz; Lyons, Leslie A et al. (2009) Chromosomal instability in rhesus macaque preimplantation embryos. Fertil Steril 91:1230-7|
|Dupont, Cathérine; Bavister, Barry D; Armant, D Randall et al. (2009) Rhesus macaque embryos derived from MI oocytes maturing after retrieval display high rates of chromosomal anomalies. Hum Reprod 24:929-35|
|Lonergan, Thomas; Brenner, Carol; Bavister, Barry (2006) Differentiation-related changes in mitochondrial properties as indicators of stem cell competence. J Cell Physiol 208:149-53|
|Bavister, Barry D (2006) The mitochondrial contribution to stem cell biology. Reprod Fertil Dev 18:829-38|
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