title: Patterning in placental 11-B hydroxysteroid dehydrogenase methylation according to prenatal socioeconomic adversity.
abstract: BACKGROUND
  Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from the maternal environment. The association of prenatal socioeconomic adversity and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal socioeconomic adversity may alter fetal response to the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal socioeconomic adversity would be associated with less HSD11B2 methylation.
  
  
  RESULTS
  We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 444 healthy term newborn infants and several markers of prenatal socioeconomic adversity: maternal education, poverty, dwelling crowding, tobacco use and cumulative risk. We also examined whether such associations were sex-specific. We found that infants whose mothers experienced the greatest levels of socioeconomic adversity during pregnancy had the lowest extent of placental HSD11B2 methylation, particularly for males. Associations were maintained for maternal education when adjusting for confounders (p<0.05).
  
  
  CONCLUSIONS
  Patterns of HSD11B2 methylation suggest that environmental cues transmitted from the mother during gestation may program the developing fetus's response to an adverse postnatal environment, potentially via less exposure to cortisol during development. Less methylation of placental HSD11B2 may therefore be adaptive and promote the effective management of stress associated with social adversity in a postnatal environment.
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
authors.forename: Allison A
authors.initials: AA
authors.lastname: Appleton
authors.forename: David A
authors.initials: DA
authors.lastname: Armstrong
authors.forename: Corina
authors.initials: C
authors.lastname: Lesseur
authors.forename: Joyce
authors.initials: J
authors.lastname: Lee
authors.forename: James F
authors.initials: JF
authors.lastname: Padbury
authors.forename: Barry M
authors.initials: BM
authors.lastname: Lester
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics*; D000328:Adult; D019175:DNA Methylation; D005260:Female; D054625:Healthcare Disparities; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011295:Prenatal Care / Q000706:statistics & numerical data*; D011297:Prenatal Exposure Delayed Effects; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D012737:Sex Factors; D012907:Smoking; D012923:Social Class
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human
references.citation: Pediatrics. 2012 Jan;129(1):e68-73
references.pmid: 22144695
references.citation: Psychiatr Clin North Am. 2010 Jun;33(2):357-73
references.pmid: 20385342
references.citation: BMC Pediatr. 2003 Dec 16;3:13
references.pmid: 14678563
references.citation: Clin Sci (Lond). 1998 Aug;95(2):115-28
references.pmid: 9680492
references.citation: JAMA. 2005 Dec 14;294(22):2879-88
references.pmid: 16352796
references.citation: Circulation. 2013 Feb 26;127(8):905-12
references.pmid: 23339873
references.citation: Endocrinology. 2001 May;142(5):1692-702
references.pmid: 11316731
references.citation: Annu Rev Nutr. 2007;27:363-88
references.pmid: 17465856
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17253-60
references.pmid: 23045638
references.citation: Psychol Bull. 2002 Mar;128(2):330-66
references.pmid: 11931522
references.citation: Psychosom Med. 2010 Feb;72(2):148-55
references.pmid: 20064905
references.citation: Early Hum Dev. 2011 Nov;87(11):729-33
references.pmid: 21975277
references.citation: PLoS One. 2012;7(6):e39791
references.pmid: 22761903
references.citation: Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1526-33
references.pmid: 17264224
references.citation: Ann N Y Acad Sci. 2010 Feb;1186:146-73
references.pmid: 20201872
references.citation: Front Biosci (Elite Ed). 2011 Jan 01;3(2):690-700
references.pmid: 21196344
references.citation: Transl Psychiatry. 2011 Jul 19;1:e21
references.pmid: 22832523
references.citation: Brain Behav Immun. 2009 Oct;23(7):905-16
references.pmid: 19217937
references.citation: Dev Neurosci. 2009;31(1-2):23-35
references.pmid: 19372684
references.citation: J Clin Invest. 2004 Oct;114(8):1146-57
references.pmid: 15489962
references.citation: Epigenetics. 2013 Jan;8(1):23-7
references.pmid: 23196856
references.citation: Dialogues Clin Neurosci. 2005;7(2):103-23
references.pmid: 16262207
references.citation: PLoS One. 2012;7(5):e37002
references.pmid: 22590643
references.citation: Front Behav Neurosci. 2009 Sep 07;3:19
references.pmid: 19826624
references.citation: Paediatr Perinat Epidemiol. 2000 Jul;14(3):194-210
references.pmid: 10949211
references.citation: Placenta. 2006 Feb-Mar;27(2-3):171-80
references.pmid: 16338462
references.citation: J Health Econ. 2005 Mar;24(2):365-89
references.pmid: 15721050
references.citation: Neuroscience. 2011 Apr 28;180:105-10
references.pmid: 21335068
references.citation: Ann N Y Acad Sci. 1999;896:131-44
references.pmid: 10681894
references.citation: Nat Rev Neurosci. 2010 Sep;11(9):651-9
references.pmid: 20725096
references.citation: Epigenetics. 2012 Aug;7(8):853-7
references.pmid: 22810058
references.citation: Am J Public Health. 2005 Aug;95(8):1396-402
references.pmid: 15985645
references.citation: Nat Neurosci. 2004 Aug;7(8):847-54
references.pmid: 15220929
references.citation: Am Psychol. 1994 Jan;49(1):15-24
references.pmid: 8122813
references.citation: Am J Hum Biol. 2007 Jan-Feb;19(1):1-19
references.pmid: 17160980
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Dec;295(6):R1941-52
references.pmid: 18971349
references.citation: Front Neuroendocrinol. 2011 Aug;32(3):265-86
references.pmid: 21144857
references.citation: Atherosclerosis. 2008 Aug;199(2):323-7
references.pmid: 18178212
references.citation: Endocrinology. 2012 Nov;153(11):5500-11
references.pmid: 22919064
references.citation: Psychoneuroendocrinology. 2012 Jun;37(6):818-26
references.pmid: 22001010
references.citation: Ann N Y Acad Sci. 2011 May;1226:14-33
references.pmid: 21615751
references.citation: CMAJ. 2007 Sep 11;177(6):583-90
references.pmid: 17846440
references.citation: Epigenomics. 2011 Jun;3(3):267-77
references.pmid: 22122337
references.citation: PLoS One. 2012;7(3):e33794
references.pmid: 22432047