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Early post-conception maternal cortisol, children’s HPAA activity and DNA methylation profiles

Part of: A Canadian perspective on DOHaD

Published online by Cambridge University Press:  15 November 2018

C. K. Barha ,
K. G. Salvante ,
M. J. Jones ,
P. Farré ,
J. Blais ,
M. S. Kobor ,
L. Zeng ,
E. Emberly  and
P. A. Nepomnaschy
C. K. Barha
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
K. G. Salvante
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
M. J. Jones
Affiliation:
Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
P. Farré
Affiliation:
Department of Physics, Simon Fraser University, Burnaby, BC, Canada
J. Blais
Affiliation:
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
M. S. Kobor
Affiliation:
Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
L. Zeng
Affiliation:
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
E. Emberly
Affiliation:
Department of Physics, Simon Fraser University, Burnaby, BC, Canada
P. A. Nepomnaschy
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada Crawford Laboratory of Evolutionary Studies, Simon Fraser University, Burnaby, BC, Canada
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Abstract

The hypothalamic–pituitary–adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms’ first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children’s pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children’s FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps<0.05), with some sex-related differences. We investigated whether epigenetic mechanisms statistically mediated these links and, therefore, could provide cues as to possible biological pathways involved. EPC cortisol was associated with >5% change in children’s buccal epithelial cells’ DNA methylation for 867 sites, while children’s HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children’s HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children’s HPAA activity.

Keywords

child developmentcortisolDNA methylationearly post-conceptionhypothalamic–pituitary–adrenal axissex differences
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Special Issue 1: Themed Issue: Canada / Indigenous Populations , February 2019 , pp. 73 - 87
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

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Footnotes

a

Current address: Faculty of Medicine, Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada

b

Current address: Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

†

Both authors contributed equally to this work

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