Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes

Simple item page
dc.contributor.authorYao, Youli
dc.contributor.authorRobinson, Alexandra M.
dc.contributor.authorZucchi, Fabiola C. R.
dc.contributor.authorRobbins, Jerrah C.
dc.contributor.authorBabenko, Olena M.
dc.contributor.authorKovalchuk, Olga
dc.contributor.authorKovalchuk, Igor
dc.contributor.authorOlson, David M.
dc.contributor.authorMetz, Gerlinde A. S.
dc.date.accessioned2014-08-26T21:16:15Z
dc.date.available2014-08-26T21:16:15Z
dc.date.issued2014
dc.descriptionSherpa Romeo green journal: open accessen_US
dc.description.abstractAbstract 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.description.peer-reviewYesen_US
dc.identifier.citationYao, 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/s12916-014-0121-6en_US
dc.identifier.urihttps://hdl.handle.net/10133/3490
dc.language.isoen_CAen_US
dc.publisherBioMed Centralen_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.publisher.institutionUniversity of Lethbridgeen_US
dc.publisher.institutionUniversity of Albertaen_US
dc.subjectPreterm birthen_US
dc.subjectMaternal stressen_US
dc.subjectPrenatal stressen_US
dc.subjectTransgenerational inheritanceen_US
dc.subjectMicroRNAen_US
dc.subjectEpigenetic regulationen_US
dc.subjectGestationen_US
dc.subjectMaternal healthen_US
dc.subjectBehavioural developmenten_US
dc.subjectPerinatal programmingen_US
dc.subjectPregnancyen_US
dc.titleAncestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomesen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
s12916-014-0121-6.pdf
Size:
1.37 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.63 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Kovalchuk, Igor
Kovalchuk, Olga
Metz, Gerlinde