Abstract / Summary
Abstract The placenta regulates foetal exposure to glucocorticoids through local cortisol metabolism and glucocorticoid receptor signalling. Key components of this pathway include 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and type 2 (11β-HSD2), and the glucocorticoid receptor (GR). This study investigated whether maternal characteristics and perinatal factors are associated with placental DNA methylation status at selected glucocorticoid-pathway loci, including HSD11B1 , HSD11B2 , and NR3C1 , in physiological term pregnancies. Placental samples were obtained from 70 term singleton pregnancies. DNA methylation was quantified by methylation‑specific qPCR and expressed as a demethylation index (DMI). Delivery mode was not associated with placental DMI of HSD11B1 , HSD11B2 island 1 and island 2, or NR3C1 . Instead, several nominal gene- and locus-specific associations were observed with maternal weight-related variables. HSD11B1 DMI showed a nominal positive association with gestational weight gain, whereas HSD11B2 DMI at both CpG islands showed distinct nominal associations with pre-pregnancy BMI and gestational weight gain. NR3C1 DMI was nominally associated with BMI at delivery only in vaginal deliveries. Delivery mode was not associated with DMI markers at the analysed glucocorticoid-pathway loci. Maternal weight-related variables showed nominal associations with HSD11B1 and HSD11B2 DMI, suggesting that maternal metabolic status may be relevant to placental epigenetic variation. HSD11B1 DMI was independently associated with placental 11β-HSD2 activity, whereas no DMI marker was independently associated with cord cortisol.