The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight

Biology of Reproduction
Benjamin B GreenCarmen J Marsit

Abstract

Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at six sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight. Logistic regressions correcting for potential confounding factors revealed a significant association between methylation at a single CpG site within HSD11B1 and being born large for gestational age. In addition, our analysis identified correlations between methylation and gene expression, including sex-specific transcriptional regulation of HSD11B2. Our work is one of the first comprehensive views of DNA methylation and expression in the placenta for both HSD11B types 1 and 2, linking epigenetic alterations with the regulation of fetal stress and birth weight outcomes.

References

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Citations

Oct 3, 2015·American Journal of Obstetrics and Gynecology·Vania JanuarRichard Saffery
May 21, 2016·International Journal of Endocrinology·Katarzyna KosickaFranciszek K Główka
Oct 1, 2016·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Katarzyna KosickaFranciszek Główka
Aug 3, 2018·Development and Psychopathology·Anja C Huizink, Susanne R de Rooij
Sep 27, 2019·Human Genetics·Giulia F Del GobboWendy P Robinson
Feb 13, 2016·Current Opinion in Obstetrics & Gynecology·Winnie W I Hui, Rossa W K Chiu
Sep 19, 2017·Journal of Physiology and Biochemistry·David Lorite MingotFrancisco J Sánchez-Muniz
Sep 19, 2018·Cellular and Molecular Life Sciences : CMLS·Ping ZhuKang Sun
Jul 6, 2019·Frontiers in Public Health·Alison BowmanJaclyn M Goodrich
Sep 13, 2018·Journal of Neural Transmission·Sarah Hartman, Jay Belsky
Oct 17, 2020·Biological Psychiatry : Cognitive Neuroscience and Neuroimaging·Robert FreedmanM Camille Hoffman

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Methods Mentioned

BETA
SGA
Methylation
Assay
PCR

Software Mentioned

GraphPad
Ensembl
Pyro Q - CpG
GraphPad Prism
R

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