Developmental Requirements of SWI/SNF Chromatin Remodeling Complexes in Porcine Embryos

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 DESCRIPTION (provided by applicant): Infertility affects an estimated 6 million people in the United States, roughly 10% of the population of reproductive age. Treating human infertility can involve assisted reproductive technologies, which often include in vitro fertilization and embryo culture. It is well-established that mammalian embryos produced in vitro possess reduced developmental competence as compared to embryos produced in vivo. It is also known that embryos cultured in the laboratory can display epigenetic changes (both in DNA methylation and covalent histone modifications), aberrant gene expression and perturbed patterns of fetal growth. Despite the known links between in vitro embryo manipulation and perturbed epigenetic and transcriptional states, very little is known about the mechanisms by which epigenetic changes are mediated in cleavage stage embryos and how these epigenetic changes lead to developmental failure. To move toward the long term goal of improving the outcome for human embryos manipulated in vitro, two specific aims are addressed in this proposal; the aims are as follows: 1) Determine the mechanism by which SWI/SNF chromatin remodeling subunits access the nuclei of porcine oocytes and blastomeres of cleavage stage embryos, and 2) determine the developmental requirements of discrete SWI/SNF chromatin remodeling complex subunits in cleavage stage embryos. These aims will be addressed through a series of experiments that involve abalation and overexpression approaches to determine how regulatory components of the SWI/SNF chromatin remodeling enzymes are trafficked to the nuclei in cleavage stage embryos. The porcine embryo is used as the model systems because of its physiologic similarity to the human embryo during the early stages of embryonic development. The findings from these studies will have an impact on human reproductive medicine and will lead to development of improved methods for manipulating and culturing embryos.