{"doi":"10.1101/2024.05.10.593571","title":"Associations Between Prenatal Vitamin D and Placental Gene Expression","abstract":"ABSTRACT Background Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. Objective We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort. Methods Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks’ gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA). Results The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy ( N =774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery ( N =753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including ARNT2 , BHLHE40 , 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 at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490911,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9454,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":341381,"name":"Melissa M. Melough","orcid":"0000-0003-1539-0980","position":1,"is_corresponding":false},{"id":664614,"name":"Samantha Lapehn","orcid":"0000-0001-6299-7633","position":2,"is_corresponding":false},{"id":419808,"name":"James W. MacDonald","orcid":"0000-0002-7328-7626","position":3,"is_corresponding":false},{"id":321863,"name":"Theo K. Bammler","orcid":null,"position":4,"is_corresponding":false},{"id":463656,"name":"Evan J. Firsick","orcid":"0000-0001-9171-126X","position":5,"is_corresponding":false},{"id":638111,"name":"Hyo Young Choi","orcid":"0000-0002-7627-8493","position":6,"is_corresponding":false},{"id":341383,"name":"Karen J. Derefinko","orcid":"0000-0001-8589-5330","position":7,"is_corresponding":false},{"id":298926,"name":"Daniel A. Enquobahrie","orcid":"0000-0001-9844-0597","position":8,"is_corresponding":false},{"id":325488,"name":"Kecia N. Carroll","orcid":"0000-0002-6646-1374","position":9,"is_corresponding":false},{"id":275838,"name":"Kaja Z. LeWinn","orcid":"0000-0002-8245-7279","position":10,"is_corresponding":false},{"id":275836,"name":"Nicole R. Bush","orcid":"0000-0003-0217-9975","position":11,"is_corresponding":false},{"id":4148,"name":"Qi Zhao","orcid":"0000-0002-5969-6407","position":12,"is_corresponding":false},{"id":325493,"name":"Sheela Sathyanarayana","orcid":"0000-0002-1480-0397","position":13,"is_corresponding":false},{"id":664613,"name":"Alison G. Paquette","orcid":"0000-0002-6065-9398","position":14,"is_corresponding":false},{"id":784497,"name":"Mariana Parenti","orcid":"0000-0003-4052-176X","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:08:41.211111Z","pmid":"38765981","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}