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Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation.

ABSTRACT: The placenta is an important organ in pregnancy, however, very little is understood about placental development at a molecular level. This includes the role of epigenetic mechanisms and how they change throughout gestation. DNA methylation studies in this organ are complicated by the different cell types that make up the placenta, each with their own unique transcriptome and epigenome. Placental dysfunction is often associated with pregnancy complications such as preeclampsia (PE). Aberrant DNA methylation in the placenta has been identified in pregnancy complications. We used immunohistochemistry (IHC) and immunofluorescence (IF) to localize 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in placenta tissue from first and second trimester as well as uncomplicated term and PE samples. IHC analysis of whole placental tissues showed 5-mC increased across gestation. When cytotrophoblasts (CTB) and syncytiotrophoblasts (STB) were isolated and assessed using IF, both 5-mC and 5-hmC increased in term CTBs compared to first/second-trimester samples. Staining intensity of 5-hmC was higher in first/second trimester STBs compared to CTBs (P = 0.0011). Finally, IHC staining of term tissue from PE and uncomplicated pregnancies revealed higher 5-mC staining intensity in placentas from PE pregnancies (P = 0.028). Our study has shown increased 5-mC and 5-hmC staining intensities across gestation and differed between two trophoblast populations. Differences in DNA methylation profiles between placental cell types may be indicative of different functions and requires further study to elucidate what changes accompany placental pathologies.

SUBMITTER: Wilson RL

PROVIDER: S-EPMC6557593 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation.

Wilson Rebecca L RL François Maxime M Jankovic-Karasoulos Tanja T McAninch Dale D McCullough Dylan D Leifert Wayne R WR Roberts Claire T CT Bianco-Miotto Tina T

Epigenetics 20190430 7

The placenta is an important organ in pregnancy, however, very little is understood about placental development at a molecular level. This includes the role of epigenetic mechanisms and how they change throughout gestation. DNA methylation studies in this organ are complicated by the different cell types that make up the placenta, each with their own unique transcriptome and epigenome. Placental dysfunction is often associated with pregnancy complications such as preeclampsia (PE). Aberrant DNA ...[more]

PMID: 31038385

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Project description:BackgroundNoninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known.PurposeTo derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion-related parameters and IPD.Study typeProspective.PopulationEighty-four women completed two pCASL MRI scans (first; 14-18 weeks and second; 19-24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD.Field strength/sequence3T/T2 -weighted half-Fourier single-shot turbo spin-echo (HASTE) and pCASL.AssessmentFour perfusion-related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation.Statistical testsComparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests.ResultsThe difference between the first and second MRI scans was statistically significant for volume (156.6 cm3 vs. 269.7 cm3 , P < 0.001) and PBF (104.9 ml/100g/min vs. 111.3 ml/100g/min, P = 0.02) for normal subjects, indicating an increase in pregnancy with advancing gestation. Of the parameters tested, the difference between the normal and IPD subjects was most pronounced in hPBF (278.1 ml/100g/min vs. 180.7 ml/100g/min, P < 0.001) and relative hPBF (259.1% vs. 183.2%, P < 0.001) at 16 weeks.Data conclusionThe high perfusion-related image parameters for IPD were significantly decreased from normal pregnancy at 14-18 weeks of gestation.Level of evidence2 TECHNICAL EFFICACY STAGE: 1 J. Magn. Reson. Imaging 2020;51:1247-1257.

Dataset Information

Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation.

Publications

Characterization of 5-methylcytosine and 5-hydroxymethylcytosine in human placenta cell types across gestation.

Similar Datasets

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