Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice
Abstract Maternal stress programs offspring disease in a sexually dimorphic manner with males often more adversely affected. Previous studies of maternal glucocorticoid exposure suggest male vulnerability may derive from placental alterations. The hexosamine signalling pathway and O-linked glycosyla...
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Nature Portfolio
2017-05-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-01666-8 |
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author | Marie Pantaleon Sarah E. Steane Kathryn McMahon James S. M. Cuffe Karen M. Moritz |
author_facet | Marie Pantaleon Sarah E. Steane Kathryn McMahon James S. M. Cuffe Karen M. Moritz |
author_sort | Marie Pantaleon |
collection | DOAJ |
description | Abstract Maternal stress programs offspring disease in a sexually dimorphic manner with males often more adversely affected. Previous studies of maternal glucocorticoid exposure suggest male vulnerability may derive from placental alterations. The hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are part of an essential adaptive survival response in healthy cells. The key enzyme involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently identified as a sex-specific placental biomarker of maternal stress. Using a mouse model of maternal corticosterone (Cort) exposure, we examined components of hexosamine biosynthesis/signalling and O-GlcNAcylation in whole placentae at E14.5. Our results demonstrate sex-specific differences in OGT levels and O-GlcNAcylation during Cort exposure which impacts on key mediators of cell survival, in particular AKT as well as the stress responsive OGT/GR transrepression complex. In male placentae only, Cort exposure increased Akt O-GlcNacylation which correlated with decreased phosphorylation. Female placentae had higher basal OGT and OGT/GR complex compared with male placentae. Cort exposure did not alter these levels in female placentae but increased global O-GlcNacylation. In male placentae Cort increased OGT and OGT/GR complex with no change in global O-GlcNacylation. These findings suggest that sex-specific differences in placental OGT play a key role in the sexually dimorphic responses to stress. |
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spelling | doaj.art-47200b0bb25a44ee8394b538d7895a3c2022-12-21T19:10:56ZengNature PortfolioScientific Reports2045-23222017-05-017111310.1038/s41598-017-01666-8Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in miceMarie Pantaleon0Sarah E. Steane1Kathryn McMahon2James S. M. Cuffe3Karen M. Moritz4School of Biomedical Sciences, The University of QueenslandSchool of Biomedical Sciences, The University of QueenslandSchool of Biomedical Sciences, The University of QueenslandSchool of Biomedical Sciences, The University of QueenslandSchool of Biomedical Sciences, The University of QueenslandAbstract Maternal stress programs offspring disease in a sexually dimorphic manner with males often more adversely affected. Previous studies of maternal glucocorticoid exposure suggest male vulnerability may derive from placental alterations. The hexosamine signalling pathway and O-linked glycosylation (O-GlcNAcylation) are part of an essential adaptive survival response in healthy cells. The key enzyme involved is O-linked-N-acetylglucosamine transferase (OGT), a gene recently identified as a sex-specific placental biomarker of maternal stress. Using a mouse model of maternal corticosterone (Cort) exposure, we examined components of hexosamine biosynthesis/signalling and O-GlcNAcylation in whole placentae at E14.5. Our results demonstrate sex-specific differences in OGT levels and O-GlcNAcylation during Cort exposure which impacts on key mediators of cell survival, in particular AKT as well as the stress responsive OGT/GR transrepression complex. In male placentae only, Cort exposure increased Akt O-GlcNacylation which correlated with decreased phosphorylation. Female placentae had higher basal OGT and OGT/GR complex compared with male placentae. Cort exposure did not alter these levels in female placentae but increased global O-GlcNacylation. In male placentae Cort increased OGT and OGT/GR complex with no change in global O-GlcNacylation. These findings suggest that sex-specific differences in placental OGT play a key role in the sexually dimorphic responses to stress.https://doi.org/10.1038/s41598-017-01666-8 |
spellingShingle | Marie Pantaleon Sarah E. Steane Kathryn McMahon James S. M. Cuffe Karen M. Moritz Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice Scientific Reports |
title | Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
title_full | Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
title_fullStr | Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
title_full_unstemmed | Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
title_short | Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
title_sort | placental o glcnac transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice |
url | https://doi.org/10.1038/s41598-017-01666-8 |
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