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Muscle Segment Homeobox Genes Direct Embryonic Diapause by Limiting Inflammation in the Uterus Public Deposited

https://ir.library.oregonstate.edu/concern/articles/8p58pf85q

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. This research was originally published in Journal of Biological Chemistry 2015. Vol:290(24): 15337-15349 © the American Society for Biochemistry and Molecular Biology.

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  • Embryonic diapause is a reproductive strategy widespread in the animal kingdom. This phenomenon is defined by a temporary arrest in blastocyst growth and metabolic activity within a quiescent uterus without implantation until the environmental and maternal milieu become favorable for pregnancy to progress. We found that uterine Msx expression persists during diapause across species; their inactivation in the mouse uterus results in termination of diapause with the development of implantation-like responses (“pseudoimplantation”) that ultimately succumbed to resorption. To understand the cause of this failure, we compared proteome profiles between floxed and Msx-deleted uteri. In deleted uteri, several functional networks, including transcription/translation, ubiquitin-proteasome, inflammation, and endoplasmic reticulum stress, were dysregulated. Computational modeling predicted intersection of these pathways on an enhanced inflammatory signature. Further studies showed that this signature was reflected in increased phosphorylated IκB levels and nuclear NFκB in deleted uteri. This was associated with enhanced proteasome activity and endoplasmic reticulum stress. Interestingly, treatment with anti-inflammatory glucocorticoid (dexamethasone) reduced the inflammatory signature with improvement of the diapause phenotype. These findings highlight an unexpected role of uterine Msx in limiting aberrant inflammatory responses to maintain embryonic diapause.
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  • Cha, J., Burnum-Johnson, K. E., Bartos, A., Li, Y., Baker, E. S., Tilton, S. C., ... & Dey, S. K. (2015). Muscle segment homeobox genes direct embryonic diapause by limiting inflammation in the uterus. Journal of Biological Chemistry, 290(24), 15337-15349. doi:10.1074/jbc.M115.655001
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  • This work was supported in part by National Institutes of Health Grants R01ES022190, U01CA184783-01, R01HD068524, and P01CA77839. This work was also supported in part by the Laboratory Directed Research and Development Program at the Pacific Northwest National Laboratory (operated by Battelle for the Department of Energy under Contract DE-AC05-76RL01830), a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science; grants from the Astellas Foundation for Research on Metabolic Disorders, the Cell Science Research Foundation, the Tokyo Biochemical Research Foundation, and the Nakatomi Foundation (to Y. H.); grants the March of Dimes (to S. K. D.); and National Research Service Award Fellowship F30AG040858 of the University of Cincinnati Medical Scientist Training Program (to J. C.).
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-08-24T18:19:44Z (GMT) No. of bitstreams: 2 TiltonSusanEnvironMoleToxMuscleSegmentHomeobox.pdf: 5904136 bytes, checksum: d6ba7704bdbbde9ff13ad8b3e5e29283 (MD5) TiltonSusanEnvironMoleToxMuscleSegmentHomeoboxSupplementalDataset.xlsx: 13551718 bytes, checksum: 34bfd913e8a8eb92f1cbb56771c7f39d (MD5)
  • description.provenance : Submitted by Patricia Black (patricia.black@oregonstate.edu) on 2015-08-24T18:18:55Z No. of bitstreams: 2 TiltonSusanEnvironMoleToxMuscleSegmentHomeobox.pdf: 5904136 bytes, checksum: d6ba7704bdbbde9ff13ad8b3e5e29283 (MD5) TiltonSusanEnvironMoleToxMuscleSegmentHomeoboxSupplementalDataset.xlsx: 13551718 bytes, checksum: 34bfd913e8a8eb92f1cbb56771c7f39d (MD5)
  • description.provenance : Made available in DSpace on 2015-08-24T18:19:44Z (GMT). No. of bitstreams: 2 TiltonSusanEnvironMoleToxMuscleSegmentHomeobox.pdf: 5904136 bytes, checksum: d6ba7704bdbbde9ff13ad8b3e5e29283 (MD5) TiltonSusanEnvironMoleToxMuscleSegmentHomeoboxSupplementalDataset.xlsx: 13551718 bytes, checksum: 34bfd913e8a8eb92f1cbb56771c7f39d (MD5) Previous issue date: 2015-06-12

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