Abstract
Background
Gestational diabetes mellitus (GDM), a type of diabetes that occurs for the first time during pregnancy, may predispose the development of chronic degenerative diseases and metabolic alterations in mother and offspring. DNA methylation and microRNA (miRNA) expression are regulatory mechanisms of gene expression that may contribute to the pathogenesis of GDM. Therefore, we determined global DNA methylation and miR-126-3p expression levels in 8 and 7 Mexican women with and without GDM, respectively.
Methods and results
Global DNA methylation was assessed by measuring the percentage of 5-methylcytosine (5-mC) in placenta, umbilical cord, and plasma DNA samples, whereas miR-126-3p expression was quantified by real-time PCR using the 2−ΔCt method of the corresponding RNA samples. A significant increase in the percentage of 5-mC was detected in placenta samples from GDM patients compared to healthy women, while plasma samples showed a significant decrease. Conversely, miR-126-3p expression levels were significantly higher in plasma from the GDM group, while placenta and umbilical cord samples showed no significant differences across experimental groups. Furthermore, DNA methylation correlated significantly with glucose levels in placenta and plasma. Likewise, miR-126-3p expression correlated significantly with plasma glucose, in addition to maternal body mass index (BMI at first trimester).
Conclusion
The results indicate that GDM is associated with alterations in global DNA methylation levels and miR-126-3p expression in placenta and/or plasma, providing insights into future novel approaches to diagnose and/or prevent this pathology.
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Data Availability
Data supporting reported results are provided as supplementary files. The following supplementary materials are included: supplementary figure S1: methodological approach; supplementary file 1: clinical history of participants; supplementary file 2: DNA methylation data; supplementary file 3: miR-126-3p expression data; supplementary Tables S1 and S2.
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Acknowledgements
We thank Rubí Hernández-Cornejo, Yazmín Sánchez-Gutiérrez, Eunice Barraza-Ortega, Lisset Hernández-Cosio, and Daniel Fregoso-Rueda for assistance in technical and logistical aspects of the project; we are also grateful to the Board of Gynecology and Obstetrics of Mazatlan, especially Efrén Peraza-Manjarrez, Virgilio Ángeles-Zatarain, and Victor Arrenquín-Romero for their help in patient recruitment and sample collection. We also thank National Council for Science and Technology (CONACYT) and the University of California (UC MEXUS) for financial support.
Funding
This research was funded by the UC MEXUS-CONACYT Collaborative Grant CN-19-39.
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Conceptualization, A.G.G. and D.L.; methodology, A.G.G., D.L., and G.L.; formal analysis, A.G.G., D.L., and G.L.; investigation, A.G.G. and D.L.; resources, A.G.G.; writing - original draft preparation, A.G.G. and D.L.; writing - review and editing, A.G.G., G.L., T.G.G., and A.A.S.; project administration and funding acquisition, A.G.G. All authors have read and agreed to the published version of the manuscript.
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The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Ethics Committee for Research at CIAD (CEI-CIAD, approval number CE/002/2020).
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11033_2023_9005_MOESM5_ESM.xlsx
Supplementary Material 5: Table S1 (Percentage of 5-mC), and Table S2 (miR-126-3p relative expression) in placenta, umbilical cord, and plasma from GDM and Control groups
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Lizárraga, D., García-Gasca, T., Lund, G. et al. Global DNA methylation and miR-126-3p expression in Mexican women with gestational diabetes mellitus: a pilot study. Mol Biol Rep 51, 5 (2024). https://doi.org/10.1007/s11033-023-09005-z
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DOI: https://doi.org/10.1007/s11033-023-09005-z