Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm.
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ABSTRACT:
SUBMITTER: Wu Y
PROVIDER: S-EPMC6371604 | biostudies-literature | 2019 Feb
REPOSITORIES: biostudies-literature
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Analysis of two birth tissues provides new insights into the epigenetic landscape of neonates born preterm.
Wu Yonghui Y Lin Xinyi X Lim Ives Yubin IY Chen Li L Teh Ai Ling AL MacIsaac Julia L JL Tan Kok Hian KH Kobor Michael S MS Chong Yap Seng YS Gluckman Peter D PD Karnani Neerja N
Clinical epigenetics 20190211 1
<h4>Background</h4>Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) ...[more]
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Project description:BackgroundPreterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear.MethodsIn this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB.ResultsSignificant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement).ConclusionsIn summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.
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Project description:BackgroundPreterm birth is a leading cause of perinatal mortality and long-term health consequences. Epigenetic mechanisms may have been at play in preterm birth survivors, and these could be persistent and detrimental to health later in life.MethodsWe performed a genome-wide DNA methylation profiling in adult twins of premature birth to identify genomic regions under differential epigenetic regulation in 144 twins with a median age of 33 years (age range 30-36).ResultsAssociation analysis detected three genomic regions annotated to the SDHAP3, TAGLN3 and GSTT1 genes on chromosomes 5, 3 and 22 (FWER: 0.01, 0.02 and 0.04) respectively. These genes display strong involvement in neurodevelopmental disorders, cancer susceptibility and premature delivery. The three identified significant regions were successfully replicated in an independent sample of twins of even older age (median age 66, range 56-80) with similar regulatory patterns and nominal p values < 5.05e-04. Biological pathway analysis detected five significantly enriched pathways all explicitly involved in immune responses.ConclusionWe have found novel evidence associating premature delivery with epigenetic modification of important genes/pathways and revealed that preterm birth, as an early life event, could be related to differential methylation regulation patterns observable in adults and even at high ages which could potentially mediate susceptibility to age-related diseases and adult health.
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