? The effects of ooplasmic factors on genome function and development remain poorly understood, despite an extensive body of literature indicating the existence of such effects. Understanding these effects is essential for a thorough understanding of the developmental mechanisms that initiate each new life, and that direct normal growth and development. Moreover, understanding these effects has significant clinical relevance in the area of assisted reproduction technology (ART), as the treatment of human infertility continues to advance through the implementation of novel microsurgical procedures being implemented in the absence of any controlled scientific data addressing their safety or efficacy. Abundant data from mouse studies reveal the potential for epigenetic effects of 'foreign' cytoplasm on the embryonic genome, leading to effects on embryo viability or developmental abnormalities, some of which are transmitted to the next generation. This proposal addresses the biology of epigenetic programming during oocyte development and maturation, the epigenetic effects of ooplasm on the embryonic genome, the potential for aberrant epigenetic modifications arising as a result of ARTs methods for application at other stages. We will exploit a model system that is based on the existence of genetically diverse egg modifiers, which differentially modify, epigenetically, the maternal and paternal genomes. The proposed studies will provide new basic data about ooplasm-nuclear interactions as well as data relevant to the clinical application of microsurgical procedures. ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Project (R01)
Project #
5R01RR018907-04
Application #
7256888
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Rall, William F
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2007
Total Cost
$356,753
Indirect Cost
Name
Temple University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
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Cheng, Yong; Zhong, Zhisheng; Latham, Keith E (2012) Strain-specific spontaneous activation during mouse oocyte maturation. Fertil Steril 98:200-6
Mtango, Namdori R; Sutovsky, Miriam; Susor, Andrej et al. (2012) Essential role of maternal UCHL1 and UCHL3 in fertilization and preimplantation embryo development. J Cell Physiol 227:1592-603
Han, Zhiming; Cheng, Yong; Liang, Cheng-Guang et al. (2010) Nuclear transfer in mouse oocytes and embryos. Methods Enzymol 476:171-84
Han, Zhiming; Mtango, Namdori R; Zhong, Zhisheng et al. (2010) Early transcription from the maternal genome controlling blastomere integrity in mouse two-cell-stage embryos. Am J Physiol Cell Physiol 298:C1235-44
Liang, Cheng-Guang; Han, Zhiming; Cheng, Yong et al. (2009) Effects of ooplasm transfer on paternal genome function in mice. Hum Reprod 24:2718-28
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Wan, Le-Ben; Pan, Hua; Hannenhalli, Sridhar et al. (2008) Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development. Development 135:2729-38
Mtango, Namdori R; Potireddy, Santhi; Latham, Keith E (2008) Oocyte quality and maternal control of development. Int Rev Cell Mol Biol 268:223-90