Placental H3K27me3 establishes female resilience to prenatal insults
PublisherNature Publishing Group
MetadataShow full item record
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).
Disease Models, Animal
Gene Expression Profiling
Prenatal Exposure Delayed Effects
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85049404791&doi=10.1038%2fs41467-018-04992-1&partnerID=40&md5=0328137bf198099fbe3c4921c12cdd7f; http://hdl.handle.net/10713/8913
- Targeted placental deletion of OGT recapitulates the prenatal stress phenotype including hypothalamic mitochondrial dysfunction.
- Authors: Howerton CL, Bale TL
- Issue date: 2014 Jul 1
- Sex-Specific Neurodevelopmental Programming by Placental Insulin Receptors on Stress Reactivity and Sensorimotor Gating.
- Authors: Bronson SL, Chan JC, Bale TL
- Issue date: 2017 Jul 15
- The omniscient placenta: Metabolic and epigenetic regulation of fetal programming.
- Authors: Nugent BM, Bale TL
- Issue date: 2015 Oct
- O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development.
- Authors: Howerton CL, Morgan CP, Fischer DB, Bale TL
- Issue date: 2013 Mar 26
- Fetal alcohol programming of hypothalamic proopiomelanocortin system by epigenetic mechanisms and later life vulnerability to stress.
- Authors: Bekdash R, Zhang C, Sarkar D
- Issue date: 2014 Sep