Placental
DNA
Methylation of
HSD11B2
and
IGF2<
Eleanor Klibaner‐Schiff, Julienne Rutherford, Victoria deMartelly, Fe Lagardo, William Gundling, Derek E. Wildman, Nanette R. Lee, Christopher Kuzawa ABSTRACT
Objectives
The intrauterine environment exerts lasting impacts on fetal growth and development, with potential long‐term effects on later health. We examined whether placental DNA methylation at HSD11B2 and IGF2 —two key regulators of the intrauterine environment—is associated with fetal growth among participants in the Cebu Longitudinal Health and Nutrition Survey (CLHNS).
Methods
We analyzed DNA methylation in placental samples from 19 births in the CLHNS using the Illumina Infinium HumanMethylation450 BeadChip. Focusing on CpG sites within HSD11B2 and the IGF2/H19 imprinting control region (ICR), we used linear regression models adjusted for gestational age to assess associations of DNA methylation with birth weight, head circumference, length, and neonatal adiposity.
Results
Higher methylation at three CpG sites within HSD11B2 was significantly associated with reduced fetal growth: one site was associated with reduced birth weight and head circumference, and two sites were associated with shorter birth length. Within the IGF2/H19 ICR, two CpG sites were significantly associated with both increased birth weight and head circumference. Both CpGs overlapped with predicted CCCTC‐binding factor (CTCF) binding sites, consistent with known regulatory mechanisms linking increased methylation at the ICR to increased IGF2 expression.
Conclusions
These findings support the hypothesis that DNA methylation at regulatory regions of HSD11B2 and IGF2 contributes to variation in fetal growth, linking placental epigenetic patterns to birth outcomes.