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Differential expression and methylation of integrin subunit alpha 11 and thrombospondin in the amnion of preterm birth.

ABSTRACT: Objective:This study aimed to investigate the association between preterm birth and epigenetic mechanisms in the amnion. Methods:We examined the association between differentially methylated regions (DMRs) and differentially expressed genes (DEG) using a cytosine-phosphate-guanine methylation array and whole-transcriptome sequencing from the amnion (preterm birth, n=5; full term, n=5). We enrolled 35 participants for mRNA expression analysis and pyrosequencing: 16 full-term and 19 preterm subjects. We compared the association of integrin subunit alpha 11 (ITGA11) and thrombospondin 2 (THBS2) gene methylation status with mRNA expression in the amnion. Results:In the preterm birth group, methylation of ITGA11 and THBS2 genes was significantly lower (ITGA11 gene: 60.30% vs. 73.16%, P<0.05; THBS2 gene: 64.59% vs. 73.16%, P<0.05), and the expression of the genes was significantly higher than that in the full-term group (ITGA11 gene: 14.20 vs. 1.57, P<0.01; THBS2 gene: 1.18 vs. 10.34, P<0.05). Conclusion:Methylation of the ITGA11 and THBS2 genes in the amnion was associated with preterm birth. Thus, ITGA11 and THBS2 gene methylation status in the amnion may be valuable in explaining the mechanism underlying preterm birth.

SUBMITTER: Yoo JY

PROVIDER: S-EPMC6137008 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Differential expression and methylation of integrin subunit alpha 11 and thrombospondin in the amnion of preterm birth.

Yoo Jae Young JY You Young-Ah YA Kwon Eun Jin EJ Park Mi Hye MH Shim Sunah S Kim Young Ju YJ

Obstetrics & gynecology science 20180903 5

<h4>Objective</h4>This study aimed to investigate the association between preterm birth and epigenetic mechanisms in the amnion.<h4>Methods</h4>We examined the association between differentially methylated regions (DMRs) and differentially expressed genes (DEG) using a cytosine-phosphate-guanine methylation array and whole-transcriptome sequencing from the amnion (preterm birth, n=5; full term, n=5). We enrolled 35 participants for mRNA expression analysis and pyrosequencing: 16 full-term and 19 ...[more]

PMID: 30254992

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Project description:Preterm birth is a global public health crisis which results in significant neonatal and maternal mortality. Yet little is known regarding the molecular mechanisms of idiopathic spontaneous preterm birth, and we have few diagnostic markers for adequate assessment of placental development and function. Previous studies of placental pathology and our transcriptomics studies suggest a role for placental maturity in idiopathic spontaneous preterm birth. It is known that placental DNA methylation changes over gestation. We hypothesized that if placental hypermaturity is present in our samples, we would observe a unique idiopathic spontaneous preterm birth DNA methylation profile potentially driving the gene expression differences we previously identified in our placental samples. Our results indicate the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern suggesting hypermaturity. Only seven significant differentially methylated regions fitting the idiopathic spontaneous preterm birth specific (relative to the controls) profile were identified, indicating unusually high similarity in DNA methylation between idiopathic spontaneous preterm birth and term birth samples. We identified an additional 1,718 significantly methylated regions in our gestational age matched controls where the idiopathic spontaneous preterm birth DNA methylation pattern mimics the term birth methylation pattern, again indicating a striking level of similarity between the idiopathic spontaneous preterm birth and term birth samples. Pathway analysis of these regions revealed differences in genes within the WNT and Cadherin signaling pathways, both of which are essential in placental development and maturation. Taken together, these data demonstrate that the idiopathic spontaneous preterm birth samples display a hypermature methylation signature than expected given their respective gestational age which likely impacts birth timing.

Dataset Information

Differential expression and methylation of integrin subunit alpha 11 and thrombospondin in the amnion of preterm birth.

Publications

Differential expression and methylation of integrin subunit alpha 11 and thrombospondin in the amnion of preterm birth.

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