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dc.contributor.authorNugent, B.M.
dc.contributor.authorO'Donnell, C.M.
dc.contributor.authorEpperson, C.N.
dc.date.accessioned2019-04-29T19:00:58Z
dc.date.available2019-04-29T19:00:58Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85049404791&doi=10.1038%2fs41467-018-04992-1&partnerID=40&md5=0328137bf198099fbe3c4921c12cdd7f
dc.identifier.urihttp://hdl.handle.net/10713/8913
dc.description.abstractAlthough sex biases in disease presentation are well documented, the mechanisms mediating vulnerability or resilience to diseases are unknown. In utero insults are more likely to produce detrimental health outcomes for males versus females. In our mouse model of prenatal stress, male offspring experience long-term dysregulation of body weight and hypothalamic pituitary adrenal stress axis dysfunction, endophenotypes of male-biased neurodevelopmental disorders. Placental function is critical for healthy fetal development, and we previously showed that sex differences in placental O-linked N-acetylglucosamine transferase (OGT) mediate the effects of prenatal stress on neurodevelopmental programming. Here we show that one mechanism whereby sex differences in OGT confer variation in vulnerability to prenatal insults is by establishing sex-specific trophoblast gene expression patterns and via regulation of the canonically repressive epigenetic modification, H3K27me3. We demonstrate that high levels of H3K27me3 in the female placenta create resilience to the altered hypothalamic programming associated with prenatal stress exposure. Copyright 2018 The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41467-018-04992-1en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subjectAnimalsen_US
dc.subjectBody Weighten_US
dc.subjectDisease Models, Animalen_US
dc.subjectEmbryo, Mammalianen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectFemaleen_US
dc.subjectFetal Developmenten_US
dc.subjectGene Expression Profilingen_US
dc.subjectGenes, X-Linkeden_US
dc.subjectHistone Codeen_US
dc.subjectHistonesen_US
dc.subjectHumansen_US
dc.subjectHypothalamo-Hypophyseal Systemen_US
dc.subjectMaleen_US
dc.subjectMiceen_US
dc.subjectN-Acetylglucosaminyltransferasesen_US
dc.subjectPlacentaen_US
dc.subjectPregnancyen_US
dc.subjectPrenatal Exposure Delayed Effectsen_US
dc.subjectRestraint, Physicalen_US
dc.subjectSex Factorsen_US
dc.subjectStress, Physiologicalen_US
dc.subjectTrophoblastsen_US
dc.titlePlacental H3K27me3 establishes female resilience to prenatal insultsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-018-04992-1
dc.identifier.pmid29967448


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