Placental O-GlcNAc-transferase expression and interactions with the glucocorticoid receptor are sex specific and regulated by maternal corticosterone exposure in mice

Scientific Reports
Marie PantaleonK M Moritz

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-GlcNa...Continue Reading

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Citations

Apr 22, 2018·Clinical and Experimental Pharmacology & Physiology·Pierre HofsteeJames Sm Cuffe
Oct 20, 2017·Journal of Neurochemistry·Ilhan AkanJohn A Hanover
Nov 8, 2018·Journal of Molecular Endocrinology·Bethany HartEmilyn U Alejandro
Feb 29, 2020·Journal of Neuroscience Research·Cheryl S Rosenfeld
Oct 14, 2018·Molecular Biology Reports·Jésica Flores-MartínSusana Genti-Raimondi
Sep 12, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Hayley A WilsonNeil J MacLusky
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Jul 31, 2020·Physiological Reviews·John C ChathamAdam R Wende
Jul 3, 2021·International Journal of Molecular Sciences·Mackenzie MooreEmilyn U Alejandro
Jun 19, 2021·Frontiers in Endocrinology·Jie Ning, Huixia Yang

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Methods Mentioned

BETA
glycosylation
PCR
immunoprecipitation
nuclear translocation
co-immunoprecipitation

Software Mentioned

GraphPad Prism

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