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Published on: November 11, 2014
RNA-Sequencing Reveals Gene Expression and Pathway Signatures in Umbilical Cord Blood Affected by Birth Delivery Mode
Yongjie Liu1, Kun Sun2, Yuexin Gan1
1Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092 China.
Insights
Cesarean section (CS) delivery alters offspring gene expression, impacting immune and metabolic pathways. This may explain increased risks for conditions like type I diabetes and asthma in infants born via CS.
Area of Science:
- Genomics
- Immunology
- Metabolomics
Background:
- Cesarean section (CS) is linked to increased offspring risks for various diseases, including type I diabetes, asthma, and obesity.
- The precise biological mechanisms underlying these increased health risks in infants born via CS remain largely unknown.
Purpose of the Study:
- To investigate the influence of CS on gene expression in the cord blood of newborns.
- To identify specific genes and pathways affected by CS delivery that may contribute to long-term health outcomes.
Main Methods:
- RNA sequencing was performed on cord blood from infants born via elective CS and vaginal delivery (VD).
- Analyses included single-gene analysis, gene set enrichment, co-expression networks, and protein-protein interactions.
- Key findings were validated in a larger cohort of CS and VD infants.
Main Results:
- CS significantly influenced the mRNA expression of genes involved in immune response (e.g., IL12A, INFG, IL1B, TNF) and metabolism (e.g., DLK1, CYP2A6).
- Serum levels of TNF-α and IFN-γ were significantly elevated in CS infants compared to VD infants.
- These molecular changes suggest a biological basis for CS-associated health risks.
Conclusions:
- CS delivery impacts offspring gene expression in critical immune and metabolic pathways.
- These alterations provide a potential mechanism for the increased risk of chronic diseases observed in CS-born infants.
- Identifying these gene expression changes can help develop biomarkers for assessing the future health of infants based on delivery mode.
Abstract:
Cesarean section (CS) confers increased risk of type I diabetes, asthma, inflammatory bowel disease, celiac disease, overweight and obesity, etc., in the offspring. However, the underlying mechanism remains unknown. To investigate the influence of CS on gene expression in cord blood, we have performed RNA-sequencing followed by single-gene analysis, gene set enrichment analysis, gene co-expression network analysis, and interacting genes/proteins analysis in eight full-term infants born by elective CS and eight matched vaginally delivered (VD) infants. Crucial genes identified above were further validated in another 20 CS and 20 VD infants. We found for the first time that mRNA expression of genes involved in immune response (IL12A, INFG, IL1B, TNF, MIF, IL4, CA1, IFI27, HLA-DOB and EPHB1) and metabolism (DLK1, CYP2A6 and GATM) were significantly influenced by CS. Notably, serum TNF-α and IFN-γ were remarkably up-regulated in the CS infants (p = 5.0 × 10-4 and 3.0 × 10-3, respectively) compared to the VD infants. It is biologically plausible that CS may exert adverse impacts on offspring health through influencing expression of genes in the above processes. These findings will help understand the potential underlying mechanisms of the adverse health impacts of CS and identify biomarkers for future health of offspring born with different delivery modes.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s43657-022-00086-7.
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