5839 genes changed during pregnancy (many genes were related to Vitamin D)

The Role of Vitamin D in the Transcriptional Program of Human Pregnancy

Amal Al-Garawi, Vincent J. Carey, Divya Chhabra, Hooman Mirzakhani, Jarrett Morrow, Jessica Lasky-Su, Weiliang Qiu, Nancy Laranjo, Augusto A. Litonjua, Scott T. Weiss scott.weiss@channing.harvard.edu

Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America

Unfortunately the study does not seem to distinguish # of changes in the 400 IU group vs the 4,400 IU group * Gene differences can result in 14 ng difference in vitamin D levels– Feb 2014 * 291 genes improved expression by 2000 IU of vitamin D – RCT March 2013 * Bio-available Vitamin D is reduced by half during pregnancy – Jan 2017 * 54 genes significantly affected by Vitamin D (50,000 IU weekly for 12 weeks) – May 2021 Items in both categories Pregnancy and Genes are listed here: {category} Items in both categories Pregnancy and Vitamin D Receptor gene are listed here: {category} Genetics category listing contains the following {include}

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Background: Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks.

Objective: Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels.

Design: The VDAART (Vitamin D Antenatal Asthma deduction Trial) study is a randomized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk. The trial enrolled 881 women at 10-18 weeks of gestation. Longitudinal gene expression measures were obtained on thirty pregnant women, using RNA isolated from peripheral blood samples obtained in the first and third trimesters. Differentially expressed genes were identified using significance of analysis of microarrays (SAM), and clustered using a weighted gene co-expression network analysis (WGCNA). Gene-set enrichment was performed to identify major biological pathways.

Results: Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes (FDR<0.05). Weighted gene coexpression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels. Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks.

Conclusion: Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles. These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life.

Trial Registration: clinicaltrials.gov NCT00920621

Data Availability Statement: All relevant data are within the paper and its Supporting Information files. The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE86200, available at: http:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ixeziewgpzgthkj&acc;=GSE86200.