Doctor of Philosophy
Dr. Andrew Watson
The preimplantation period of development represents the highest interval of embryonic loss throughout pregnancy. It is therefore imperative that we elucidate the mechanisms involved in regulating preimplantation embryonic responses to stress and that govern development. The MAPK pathways are involved in both responding to environmental stress and regulation of development throughout embryogenesis, and are therefore good candidates to study the mechanisms involved in preimplantation embryonic adaptation to stress and development. The preimplantation embryo culminates in the development of a fluid filled structure called the blastocyst. It is at this stage the first differentiation events occur and the trophectoderm (TE), which will go on to form the embryonic portion of the placenta, develops. The p38 MAPK is required for embryo development to proceed beyond the 8-16 cell stage as well to play an adaptive role in regulating embryonic response to culture stress. My hypothesis is that the MAPK pathways regulate expression of TE associated proteins and apoptosis in response to culture stress and may regulate expression of TE associated proteins by affecting SNAI1 and SNAI2 expression or localization during blastocyst formation. I have shown that p38 MAPK regulates Aqp3 and Aqp9 expression in response to hyperosmotic stress in the blastocyst. I have also demonstrated that p38 MAPK is required for blastocyst expansion and hatching and regulates tight junction permeability and TJP1 localization during blastocyst formation. The p38 MAPK pathway also affects Aqp3 mRNA expression and protein detection. The p38 MAPK does not regulate apoptosis, however, the JNK/SAPK pathway does. I have demonstrated that two transcription factors, Snai1 and Snai2, which are downstream targets of the p38 MAPK pathway, are present throughout preimplantation development. In other cell types, SNAI1 and SNAI2 regulate many genes involved in blastocyst formation. I have shown that in the preimplantation embryo, SNAI1 and SNAI2 have a unique asymmetric distribution pattern from the 2-cell to 8-cell stage, and are then segregated to the TE of the blastocyst. These results suggest that SNAI1 and SNAI2 may be involved in TE differentiation or regulation. Taken together, this data reveal the contributions of p38 MAPK to the regulation of preimplantation development.
Bell, Christine E., "The Developmental and Adaptive role of Mitogen Activated Protein Kinase Pathways During Preimplantation Development" (2012). Electronic Thesis and Dissertation Repository. 402.