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Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life

BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to i...

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Autores principales: Tilley, Sloane K., Martin, Elizabeth M., Smeester, Lisa, Joseph, Robert M., Kuban, Karl C. K., Heeren, Tim C., Dammann, Olaf U., O’Shea, T. Michael, Fry, Rebecca C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841757/
https://www.ncbi.nlm.nih.gov/pubmed/29513726
http://dx.doi.org/10.1371/journal.pone.0193271
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author Tilley, Sloane K.
Martin, Elizabeth M.
Smeester, Lisa
Joseph, Robert M.
Kuban, Karl C. K.
Heeren, Tim C.
Dammann, Olaf U.
O’Shea, T. Michael
Fry, Rebecca C.
author_facet Tilley, Sloane K.
Martin, Elizabeth M.
Smeester, Lisa
Joseph, Robert M.
Kuban, Karl C. K.
Heeren, Tim C.
Dammann, Olaf U.
O’Shea, T. Michael
Fry, Rebecca C.
author_sort Tilley, Sloane K.
collection PubMed
description BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. STUDY DESIGN: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated. RESULTS: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. CONCLUSION: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD).
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spelling pubmed-58417572018-03-23 Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life Tilley, Sloane K. Martin, Elizabeth M. Smeester, Lisa Joseph, Robert M. Kuban, Karl C. K. Heeren, Tim C. Dammann, Olaf U. O’Shea, T. Michael Fry, Rebecca C. PLoS One Research Article BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. STUDY DESIGN: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84). The association between the identified differentially methylated CpG sites and neurocognitive outcome at ten years of age was then evaluated. RESULTS: Spontaneous EPTB was associated with differential CpG methylation levels in 250 CpG sites (217 unique genes) with the majority displaying hypermethylation. The identified genes are known to play a role in neurodevelopment and are enriched for basic helix-loop-helix transcription factor binding sites. The placental CpG methylation levels for 17 of these sites predicted cognitive function at ten years of age. CONCLUSION: A hypermethylation signature is present in DNA from placentas in infants with spontaneous EPTB. CpG methylation levels of critical neurodevelopment genes in the placenta predicted later life cognitive function, supporting the developmental origins of health and disease hypothesis (DOHaD). Public Library of Science 2018-03-07 /pmc/articles/PMC5841757/ /pubmed/29513726 http://dx.doi.org/10.1371/journal.pone.0193271 Text en © 2018 Tilley et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Tilley, Sloane K.
Martin, Elizabeth M.
Smeester, Lisa
Joseph, Robert M.
Kuban, Karl C. K.
Heeren, Tim C.
Dammann, Olaf U.
O’Shea, T. Michael
Fry, Rebecca C.
Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title_full Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title_fullStr Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title_full_unstemmed Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title_short Placental CpG methylation of infants born extremely preterm predicts cognitive impairment later in life
title_sort placental cpg methylation of infants born extremely preterm predicts cognitive impairment later in life
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841757/
https://www.ncbi.nlm.nih.gov/pubmed/29513726
http://dx.doi.org/10.1371/journal.pone.0193271
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