https://orcid.org/0000-0001-7776-2378
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Abstract
Background: We performed an epigenome-wide longitudinal DNA methylation study on an Indian cohort of pregnant women, GARBH-Ini, at three time points during pregnancy and at delivery. Aim & objective: Our aim was to identify temporal DNA methylation changes in maternal peripheral blood during the period of gestation and assess their impact on biological pathways critical for term delivery. Results: Significantly differentially methylated CpGs were identified by linear mixed model analysis (Bonferroni p < 0.01) and classified into two distinct temporal methylation trends: increasing and decreasing during gestation. Genes with upward methylation trend were enriched for T-cell activity, while those with a downward trend were enriched for solute transport and cell structure organization functions. Conclusion: Consistent trends of DNA methylation in maternal peripheral blood point to the sentinel function of T cells in the maintenance of pregnancy, and the importance of coordinated cellular remodeling to facilitate term delivery.
Plain language summary
DNA methylation is the addition of a methyl group to the molecular structure of DNA, which then alters the gene expression. The goal of the study was to find out how DNA methylation patterns change over time during pregnancy and how these changes are related to the biological processes that are important for the delivery of a healthy baby at full term. Using statistical modeling, we identified specific patterns of DNA methylation changes during pregnancy and classified them into two groups based on the direction of the changes. The genes associated with increasing methylation levels were related to the activities of T cells, which are important for the immune system. The genes associated with decreasing methylation levels were related to processes like transporting substances and organizing cell structures. In conclusion, our findings suggest that T cells play an important role in maintaining a healthy pregnancy, and the study highlights the importance of coordinated changes in cells to support a successful delivery of a baby at term.
Tweetable abstract
Study on Indian women during pregnancy reveals DNA methylation changes over time. Changes related to T cells and cellular remodeling found to be important for term delivery #PregnancyResearch #DNAMethylation @Garbhinicohort @DBTindia @FollowDbtNibmg @THSTIFaridabad
Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0145
J Das planned and analyzed the data and wrote the manuscript. R Thiruvengadam collated the clinical data of the study participants. S Bhatnagar, P Majumder, A Maitra, R Thiruvengadam and U Natchu conceptualized the study cohort. A Maitra, P Majumder and S Bhatnagar substantively revised the manuscript. P Kshetrapal, R Thiruvengadam and N Wadhwa assisted in biospecimen storage, identification and shipment. The GARBH-Ini Team developed and implemented the clinical data collection methods and data management procedures in the GARBH-Ini cohort. P Majumder and A Maitra have accessed the data and verified the underlying data reported in the manuscript. All authors confirm that they have full access to all the data in the study and accept responsibility to submit for publication. All authors read and approved the final manuscript.
Acknowledgments
Professor M Bhan will always be remembered reverently for his critical scientific and technical feedback. The authors recognize the efforts of the personnel of the GARBH-Ini Cohort and laboratory support from the Core Technologies Research Initiative (CoTeRI). This work was funded by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India (BT/PR9983/MED/97/194/2013) and for some components of the biorepository by the Grand Challenges India – All Children Thriving Program (supported by the Programme Management Unit), Biotechnology Industry Research Assistance Council (BIRAC/GCI/0114/03/14–ACT). The authors are thankful to S Sinha and A Gambhir for their technical feedback and support, and would also like to thank S Ghosh of NIBMG for assistance on submission of the data in GEO.
Financial & competing interests disclosure
This work was funded by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India (BT/PR9983/MED/97/194/2013) and for some components of the biorepository by the Grand Challenges India – All Children Thriving Program (supported by the Programme Management Unit), Biotechnology Industry Research Assistance Council (BIRAC/GCI/0114/03/14–ACT). PP Majumder acknowledges support of his JC Bose Fellowship. J Das is supported by the Research Fellowship (NET) of the University Grants Commission (UGC), India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval for all human experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.
Data sharing statement
The data that support the findings of this study and the source codes are openly available in Gene Expression Omnibus at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216906, under the study accession number GSE216906, and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169338, under the study accession number GSE169338, and https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE234190 under the study accession number GSE234190.