(P10-077-24) Associations Between Prenatal Vitamin D and Placental Gene Expression

Objectives: Vitamin D is a hormone regulating gene transcription. In the placenta, a key functional tissue in pregnancy, vitamin D has been linked to immune and vascular function. To date, studies of vitamin D and human placental gene expression have focused on a limited number of genes. Transcriptome-wide RNA sequencing can provide a comprehensive representation of the placental effects of vitamin D. We investigated the association between prenatal vitamin D and placental gene expression in a large, prospective birth cohort.

Methods: Participants were recruited in Shelby County, Tennessee as part of the CANDLE (Conditions Affecting Neurocognitive Development and Learning in Early childhood) study. Vitamin D level was measured as plasma 25-hydroxyvitatmin D [25(OH)D] at enrollment (between 16 and 28 weeks of gestation) and delivery. Placenta samples were collected at birth, and RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) (FDR < 0.1) using adjusted linear regression analyses and conducted weighted gene coexpression network analysis (WGCNA).

Results: This analysis included 774 CANDLE participants with vitamin D and transcriptomic data. The median vitamin D level of CANDLE participants was 21.8 ng/mL 25(OH)D at enrollment (IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at enrollment, but no DEGs were associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cellular membrane trafficking, and RNA transcription and processing. Using WGCNA, we also identified 2 gene modules whose expression was associated with 25(OH)D at enrollment. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including ARNT2, FOSL2, JUND, and NFKB1.

Conclusions: Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression. Future research is needed to investigate a potential programming role of vitamin D on placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

Funding Sources: The Urban Child Institute, NIH Office of the Director, and NIH National Institute of Environmental Health Sciences.