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Published on: September 7, 2017
DNA methylation at imprint regulatory regions in preterm birth and infection
Ying Liu1, Cathrine Hoyo, Susan Murphy
1Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA.
Insights
Intrauterine infections in preterm birth may alter DNA methylation at the PLAGL1 gene, potentially increasing chronic disease risk. This epigenetic change was observed in infants with chorioamnionitis and funisitis.
Area of Science:
- Epigenetics
- Developmental Biology
- Perinatal Medicine
Background:
- Intrauterine infections are linked to preterm birth and potential long-term health issues.
- Epigenetic modifications, such as DNA methylation, play a crucial role in gene regulation and development.
- Understanding the impact of infection on fetal epigenetics is vital for predicting future health outcomes.
Purpose of the Study:
- To investigate DNA methylation patterns in preterm infants based on birth type and intrauterine infection status.
- To examine methylation at 9 differentially methylated regions regulating imprinted genes.
- To determine if infection (chorioamnionitis or funisitis) influences DNA methylation in preterm infants.
Main Methods:
- Prospective cohort study of 73 mother-infant dyads.
- Cord blood DNA methylation measured using bisulfite pyrosequencing at 9 imprinted gene regions.
- Statistical analyses (ANOVA, logistic regression) to compare methylation by preterm birth type and infection status.
Main Results:
- No significant differences in DNA methylation were found across different types of preterm birth.
- Increased PLAGL1 DNA methylation was observed in infants with chorioamnionitis compared to those without (P < .01).
- PLAGL1 DNA methylation was also elevated in infants with funisitis versus those without (P < .05).
Conclusions:
- Intrauterine infections, specifically chorioamnionitis and funisitis, are associated with altered PLAGL1 DNA methylation in preterm infants.
- Dysregulation of PLAGL1 is linked to abnormal development and cancer, suggesting potential long-term risks.
- Early-life infection/inflammation may induce epigenetic changes that predispose individuals to chronic diseases later in life.
Objective:
To aid in understanding long-term health consequences of intrauterine infections in preterm birth, we evaluated DNA methylation at 9 differentially methylated regions that regulate imprinted genes by type of preterm birth (spontaneous preterm labor, preterm premature rupture of membranes, or medically indicated [fetal growth restriction and preeclampsia]) and infection status (chorioamnionitis or funisitis).
Study Design:
Data on type of preterm birth and infection status were abstracted from medical records and standardized pathology reports in 73 preterm infants enrolled in the Newborn Epigenetics STudy, a prospective cohort study of mother-infant dyads in Durham, NC. Cord blood was collected at birth, and infant DNA methylation levels at the H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, and PLAGL1 differentially methylated regions were measured using bisulfite pyrosequencing. One-way analyses of variance and logistic regression models were used to compare DNA methylation levels by type of preterm birth and infection status.
Results:
DNA methylation levels did not differ at any of the regions (P > .20) between infants born via spontaneous preterm labor (average n = 29), preterm premature rupture of membranes (average n = 17), or medically indicated preterm birth (average n = 40). Levels were significantly increased at PLAGL1 in infants with chorioamnionitis (n = 10, 64.4%) compared with infants without chorioamnionitis (n = 63, 57.9%), P < .01. DNA methylation levels were also increased at PLAGL1 for infants with funisitis (n = 7, 63.3%) compared with infants without funisitis (n = 66, 58.3%), P < .05.
Conclusion:
Dysregulation of PLAGL1 has been associated with abnormal development and cancer. Early-life exposures, including infection/inflammation, may affect epigenetic changes that increase susceptibility to later chronic disease.
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