Patterning in placental 11-beta hydroxysteroid dehydrogenase methylation according to prenatal socioeconomic adversity

Prenatal socioeconomic adversity (SA) is associated with several perinatal outcomes although the explanatory mechanisms are not well understood. Fetal development 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 fetus from this exposure. While HSD11B2 is regulated by DNA methylation and such methylation is susceptible to stressors from the maternal environment, the association of prenatal SA and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal SA may program the developing fetus to expect adversity in the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal SA would be associated with less HSD11B2 methylation. Among 445 healthy term newborns, we examined the association between methylation of placental HSD11B2 and several markers of prenatal SA: maternal education, poverty, crowded dwelling, tobacco use, cumulative SA risk. Infants whose mothers experienced the greatest levels of SA during pregnancy had the lowest placental HSD11B2 methylation extent. Associations were maintained for maternal education when adjusting for confounders (p<0.05). Patterns of HSD11B2 methylation suggest that environmental cues transmitted from the mother during gestation may program the developing fetus to expect an adverse postnatal environment, potentially via less exposure to cortisol during development. Less methylation of HSD11B2 may therefore be adaptive and promote the effective management of stress associated with social adversity in a postnatal environment.