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dc.contributor.author Yao, Youli
dc.contributor.author Robinson, Alexandra M.
dc.contributor.author Zucchi, Fabiola C. R.
dc.contributor.author Robbins, Jerrah C.
dc.contributor.author Babenko, Olena M.
dc.contributor.author Kovalchuk, Olga
dc.contributor.author Kovalchuk, Igor
dc.contributor.author Olson, David M.
dc.contributor.author Metz, Gerlinde A. S.
dc.date.accessioned 2014-08-26T21:16:15Z
dc.date.available 2014-08-26T21:16:15Z
dc.date.issued 2014
dc.identifier.citation Yao, Y., Robinson, A.M., Zucchi, F.C.R., Robbins, J.C., Babenko, O., Kovalchuk, O., ...Metz, G.A.S. (2014). Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC Medicine, 12 (121), 1-12. doi:10.1186/s12916-014-0121-6 en_US
dc.identifier.uri https://hdl.handle.net/10133/3490
dc.description Sherpa Romeo green journal: open access en_US
dc.description.abstract Abstract Background: Chronic stress is considered to be one of many causes of human preterm birth (PTB), but no direct evidence has yet been provided. Here we show in rats that stress across generations has downstream effects on endocrine, metabolic and behavioural manifestations of PTB possibly via microRNA (miRNA) regulation. Methods: Pregnant dams of the parental generation were exposed to stress from gestational days 12 to 18. Their pregnant daughters (F1) and grand-daughters (F2) either were stressed or remained as non-stressed controls. Gestational length, maternal gestational weight gain, blood glucose and plasma corticosterone levels, litter size and offspring weight gain from postnatal days 1 to 30 were recorded in each generation, including F3. Maternal behaviours were analysed for the first hour after completed parturition, and offspring sensorimotor development was recorded on postnatal day (P) 7. F0 through F2 maternal brain frontal cortex, uterus and placenta miRNA and gene expression patterns were used to identify stress-induced epigenetic regulatory pathways of maternal behaviour and pregnancy maintenance. Results: Progressively up to the F2 generation, stress gradually reduced gestational length, maternal weight gain and behavioural activity, and increased blood glucose levels. Reduced offspring growth and delayed behavioural development in the stress cohort was recognizable as early as P7, with the greatest effect in the F3 offspring of transgenerationally stressed mothers. Furthermore, stress altered miRNA expression patterns in the brain and uterus of F2 mothers, including the miR-200 family, which regulates pathways related to brain plasticity and parturition, respectively. Main miR-200 family target genes in the uterus, Stat5b, Zeb1 and Zeb2, were downregulated by multigenerational stress in the F1 generation. Zeb2 was also reduced in the stressed F2 generation, suggesting a causal mechanism for disturbed pregnancy maintenance. Additionally, stress increased placental miR-181a, a marker of human PTB. Conclusions: The findings indicate that a family history of stress may program central and peripheral pathways regulating gestational length and maternal and newborn health outcomes in the maternal lineage. This new paradigm may model the origin of many human PTB causes. en_US
dc.language.iso en_CA en_US
dc.publisher BioMed Central en_US
dc.subject Preterm birth en_US
dc.subject Maternal stress en_US
dc.subject Prenatal stress en_US
dc.subject Transgenerational inheritance en_US
dc.subject MicroRNA en_US
dc.subject Epigenetic regulation en_US
dc.subject Gestation en_US
dc.subject Maternal health en_US
dc.subject Behavioural development en_US
dc.subject Perinatal programming en_US
dc.subject Pregnancy en_US
dc.title Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Biological Sciences en_US
dc.description.peer-review Yes en_US
dc.publisher.institution University of Lethbridge en_US
dc.publisher.institution University of Alberta en_US


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