Characterization of methylation profiles in spontaneous preterm birth placental villous tissue

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 functio...

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Main Authors: Heather M. Brockway, Samantha L. Wilson, Suhas G. Kallapur, Catalin S. Buhimschi, Louis J. Muglia, Helen N. Jones
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035933/?tool=EBI
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author Heather M. Brockway
Samantha L. Wilson
Suhas G. Kallapur
Catalin S. Buhimschi
Louis J. Muglia
Helen N. Jones
author_facet Heather M. Brockway
Samantha L. Wilson
Suhas G. Kallapur
Catalin S. Buhimschi
Louis J. Muglia
Helen N. Jones
author_sort Heather M. Brockway
collection DOAJ
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.
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spelling doaj.art-5d1a23f1e0fd4f0ebd1b8b82572f7ca02023-03-26T05:31:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01183Characterization of methylation profiles in spontaneous preterm birth placental villous tissueHeather M. BrockwaySamantha L. WilsonSuhas G. KallapurCatalin S. BuhimschiLouis J. MugliaHelen N. JonesPreterm 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035933/?tool=EBI
spellingShingle Heather M. Brockway
Samantha L. Wilson
Suhas G. Kallapur
Catalin S. Buhimschi
Louis J. Muglia
Helen N. Jones
Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
PLoS ONE
title Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
title_full Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
title_fullStr Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
title_full_unstemmed Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
title_short Characterization of methylation profiles in spontaneous preterm birth placental villous tissue
title_sort characterization of methylation profiles in spontaneous preterm birth placental villous tissue
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035933/?tool=EBI
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