title: Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo.
abstract: Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which prenatal stress affects postnatal functioning. This study addresses this gap by examining the effect of chronic stress and traumatic war-related stress on epigenetic changes in four key genes regulating the HPA axis in neonatal cord blood, placenta, and maternal blood: CRH, CRHBP, NR3C1, and FKBP5. Participants were 24 mother-newborn dyads in the conflict-ridden region of the eastern Democratic Republic of Congo. BW data were collected at delivery and maternal interviews were conducted to assess culturally relevant chronic and war-related stressors. Chronic stress and war trauma had widespread effects on HPA axis gene methylation, with significant effects observed at transcription factor binding (TFB) sites in all target genes tested. Some changes in methylation were unique to chronic or war stress, whereas others were observed across both stressor types. Moreover, stress exposures impacted maternal and fetal tissues differently, supporting theoretical models that stress impacts vary according to life phase. Methylation in several NR3C1 and CRH CpG sites, all located at TFB sites, was associated with BW. These findings suggest that prenatal stress exposure impacts development via epigenetic changes in HPA axis genes.
authors.affiliation: University of Florida.
authors.forename: Darlene A
authors.initials: DA
authors.lastname: Kertes
authors.affiliation: University of Florida.
authors.forename: Hayley S
authors.initials: HS
authors.lastname: Kamin
authors.affiliation: Institute of Evolutionary Biology (CSIC-Universitat Pompeu Fabra).
authors.forename: David A
authors.initials: DA
authors.lastname: Hughes
authors.affiliation: University of Florida.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Rodney
authors.affiliation: University of Florida.
authors.forename: Samarth
authors.initials: S
authors.lastname: Bhatt
authors.affiliation: University of Florida.
authors.forename: Connie J
authors.initials: CJ
authors.lastname: Mulligan
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology; D015023:Democratic Republic of the Congo; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007231:Infant, Newborn; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D000067073:Psychological Trauma / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D002352:Carrier Proteins; D003346:Corticotropin-Releasing Hormone; D011965:Receptors, Glucocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C497713:NR3C1 protein, human; C067133:corticotropin releasing factor-binding protein
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