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Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile

Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities...

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Autores principales: Gil, Gislene Pereira, Ananina, Galina, Maschietto, Mariana, Lima, Sheila Coelho Soares, da Silva Costa, Sueli Matilde, Baptista, Leticia de Carvalho, Ito, Mirta Tomie, Costa, Fernando Ferreira, Costa, Maria Laura, de Melo, Mônica Barbosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491616/
https://www.ncbi.nlm.nih.gov/pubmed/36129958
http://dx.doi.org/10.1371/journal.pone.0274762
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author Gil, Gislene Pereira
Ananina, Galina
Maschietto, Mariana
Lima, Sheila Coelho Soares
da Silva Costa, Sueli Matilde
Baptista, Leticia de Carvalho
Ito, Mirta Tomie
Costa, Fernando Ferreira
Costa, Maria Laura
de Melo, Mônica Barbosa
author_facet Gil, Gislene Pereira
Ananina, Galina
Maschietto, Mariana
Lima, Sheila Coelho Soares
da Silva Costa, Sueli Matilde
Baptista, Leticia de Carvalho
Ito, Mirta Tomie
Costa, Fernando Ferreira
Costa, Maria Laura
de Melo, Mônica Barbosa
author_sort Gil, Gislene Pereira
collection PubMed
description Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.
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spelling pubmed-94916162022-09-22 Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile Gil, Gislene Pereira Ananina, Galina Maschietto, Mariana Lima, Sheila Coelho Soares da Silva Costa, Sueli Matilde Baptista, Leticia de Carvalho Ito, Mirta Tomie Costa, Fernando Ferreira Costa, Maria Laura de Melo, Mônica Barbosa PLoS One Research Article Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity. Public Library of Science 2022-09-21 /pmc/articles/PMC9491616/ /pubmed/36129958 http://dx.doi.org/10.1371/journal.pone.0274762 Text en © 2022 Gil et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://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
Gil, Gislene Pereira
Ananina, Galina
Maschietto, Mariana
Lima, Sheila Coelho Soares
da Silva Costa, Sueli Matilde
Baptista, Leticia de Carvalho
Ito, Mirta Tomie
Costa, Fernando Ferreira
Costa, Maria Laura
de Melo, Mônica Barbosa
Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title_full Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title_fullStr Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title_full_unstemmed Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title_short Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
title_sort epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491616/
https://www.ncbi.nlm.nih.gov/pubmed/36129958
http://dx.doi.org/10.1371/journal.pone.0274762
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