Associations Between Prenatal Vitamin D and Placental Gene Expression

Mariana Parenti; Melissa M Melough; Samantha Lapehn; James MacDonald; Theo Bammler; Evan J Firsick; Hyo Young Choi; Karen J Derefinko; Daniel A Enquobahrie; Kecia N Carroll; Kaja Z LeWinn; Nicole R Bush; Qi Zhao; Sheela Sathyanarayana; Alison G Paquette

doi:10.1016/j.tjnut.2024.10.019

Associations Between Prenatal Vitamin D and Placental Gene Expression

J Nutr. 2024 Oct 12:S0022-3166(24)01096-4. doi: 10.1016/j.tjnut.2024.10.019. Online ahead of print.

Authors

Affiliations

¹ Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States. Electronic address: Mariana.Parenti@SeattleChildrens.org.
² Department of Health Behavior and Nutrition Sciences, University of Delaware, Newark, DE, United States.
³ Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States.
⁴ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
⁵ Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States.
⁶ Department of Preventive Medicine, University of Tennessee Health Sciences Center, Memphis, TN, United States; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Sciences Center, Memphis, TN, United States.
⁷ Department of Epidemiology, University of Washington, Seattle, WA, United States.
⁸ Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
⁹ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States.
¹⁰ Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, United States; Department of Pediatrics, University of California, San Francisco, San Francisco, CA, United States.
¹¹ Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Department of Epidemiology, University of Washington, Seattle, WA, United States; Center for Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States.
¹² Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States; Department of Pediatrics, University of Washington, Seattle, WA, United States.

PMID: 39401684
DOI: 10.1016/j.tjnut.2024.10.019

Abstract

Background: Vitamin D is a hormone that regulates gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D.

Objectives: We investigated the association between prenatal vitamin D concentrations and placental gene expression in a large, prospective pregnancy cohort.

Methods: Participants were recruited from Shelby County, TN, United States, in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at midpregnancy (16-28 wk) and delivery. RNA was sequenced from placental samples collected at birth. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene coexpression network analysis.

Results: The median 25(OH)D of participants was 21.8 ng/mL at midpregnancy (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 17 DEGs was associated with 25(OH)D at midpregnancy, but only 1 DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and transcriptional regulation. We identified 2 weighted gene coexpression network analysis gene modules whose expression was associated with 25(OH)D at midpregnancy 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 and FOSL2. We also identified 12 modules associated with 25(OH)D in females and 1 module in males.

Conclusions: 25(OH)D during midpregnancy, 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 modulating placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

Keywords: 25-hydroxyvitamin D; developmental origins of health and disease; placenta; transcriptomics; vitamin D.