Patterning in Placental 11-B Hydroxysteroid Dehydrogenase Methylation According to Prenatal Socioeconomic Adversity

Abstract

BackgroundPrenatal 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.Methods and FindingsWe 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).ConclusionsPatterns 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.

Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: The multi-ethnic study of atherosclerosis

“…For example, 7 out of 8 prior studies in this area found evidence of an association between at least one measure of life course SES and DNAm, [11][12][13][14][16][17][18] which is consistent with the results of this study. Similar to Borghol et al, 11 who found little overlap in DNAm patterns associated with childhood and adult SES, we found that childhood SES was associated with DNAm in AVP, FKBP5, OXTR, CCL1, CD1D, and F8, while adult SES was associated with DNAm in a somewhat different set of genes, including AVP, CD1D, F8, KLRG1, NLRP12, and TLR3.…”

“…Perng et al 16 found that maternal education was positively associated with global DNAm in boys (but not girls) in a subset of 568 children from the Bogota School Children Cohort. Obermann-Borst et al 17 found that maternal education was associated with increased DNAm in a gene related to the insulin pathway in a sample of 120 children at 17 months of age; and Appleton et al 18 found that maternal education was associated with decreased placental DNAm in a gene related to the inactivation of maternal cortisol in a study of 444 healthy newborns.…”

Regions of variable DNA methylation in human placenta associated with newborn neurobehavior

“…This likely suggests that prenatal programming is occurring through unique genes and molecular pathways to regulate different aspects of neurobehavioral development. This is concurrent with other findings using the NNNS assessment, where different NNNS summary scores have been associated with unique and specific epigenetic patterning 10,11,13,41,42 or factors from the prenatal environment. [20][21][22][23][24][25][26][27] Quality of movement and infant attention were associated with methylation of genes involving neurological development and function, including neurotransmitter uptake, dopamine uptake involved in synaptic transmission, and dendritic spine organization.…”

Fetal lung and placental methylation is associated with in utero nicotine exposure

“…One potential mechanism is DNA methylation, and a number of studies have examined DNA methylation changes in cord blood [23][24][25][26] and placental tissue as a result of smoke exposure. [27][28][29] Decreased DNA methyltransferase 1 (DNMT1) and increased DNA methyltransferase 3b (DNMT3b) expression have been shown to occur in human small airway smooth muscle cells exposed to cigarette smoke condensate. 30 In placental tissue, Suter et al demonstrated the correlation between CYP1A1 expression and CpG methylation variation, 31 thus supporting the role of DNA methylation.…”