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Disruption of Hippo Signaling Pathway During Bovine Granulosa Cell Proliferation, Oocyte Maturation and Embryonic Development

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Title: Disruption of Hippo Signaling Pathway During Bovine Granulosa Cell Proliferation, Oocyte Maturation and Embryonic Development
Author: Sharma, Jyoti
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Madan, Pavneesh
Abstract: The Hippo signaling pathway plays an essential role during various ovarian physiological processes, with a significant role in granulosa cell proliferation, oocyte maturation and lineage segregation during the formation of a blastocyst in the mouse model. Even though our lab and a few other reports have recently established the presence of the Hippo signaling pathway components in bovine granulosa cells and embryos, the role and regulation of these components largely remains unknown in the cow. Thus, the aim of the present study was to establish the role of Hippo signaling pathway components during early bovine embryogenesis, using chemical inhibition and GapmeR specific knockdown methods. Using Cerivastatin and XMU-MP-1 treatment, significant differences were observed in the regulation of Hippo signaling pathway during the pre-compaction and post-compaction stages of bovine embryogenesis. During the pre-compaction stages, regulation of YAP1-TAZ was dependent on MST-LATS1 components of Hippo pathway, suggesting a potential role of these components in Maternal to Embryonic Transition (MET). Conversely, during the post compaction stages, YAP1 and TAZ are regulated independent of MST1-LATS1 components, suggesting blastocyst formation to be regulated in part by other cell signaling pathways in addition to the Hippo pathway effectors (YAP1 and TAZ). Additionally, the results from the Cerivastatin inhibition study suggest that bovine granulosa cell proliferation and Cumulus oocyte complex (COC) development are dependent on LATS1-YAP1/TAZ signalling molecules. However, no specific effect of Cerivastatin was observed on MST1/2, suggesting a significant role of LATS1-YAP1/TAZ signaling in bovine COC development and granulosa cell proliferation. Furthermore, a pivotal role of MST1 in maintaining granulosa cell viability and blastocyst formation in the bovine model was validated using the GapmeR specific method. The presence of Hippo signaling pathway components can thus be used to ascertain mechanisms of bovine granulosa cell proliferation, oocyte development and blastocyst formation, and in turn our improved knowledge can be used to produce healthy bovine embryos. Since cows are also an excellent model for humans, knowledge gained from these studies will also help us improve human embryo production techniques.
Date: 2021-09
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Related Publications: Sharma, J.; Antenos, M.; Madan, P. A Comparative Analysis of Hippo Signaling Pathway Components during Murine and Bovine Early Mammalian Embryogenesis. Genes 2021, 12, 281.

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