title: The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight.
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.
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: Benjamin B
authors: BB
authors: Green
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: David A
authors: DA
authors: Armstrong
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: Corina
authors: C
authors: Lesseur
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: Alison G
authors: AG
authors: Paquette
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: Dylan J
authors: DJ
authors: Guerin
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors: Lauren E
authors: LE
authors: Kwan
authors: Departments of Pharmacology and Toxicology and of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire carmen.j.marsit@dartmouth.edu.
authors: Carmen J
authors: CJ
authors: Marsit
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001724:Birth Weight / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2
keywords: developmental origins of health and disease; glucocorticoid receptor; glucocorticoids; metabolic syndrome; stress