Article

Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas

Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA.
Epigenetics: official journal of the DNA Methylation Society (Impact Factor: 5.11). 07/2011; 6(7):920-7. DOI: 10.4161/epi.6.7.16079
Source: PubMed

ABSTRACT The placenta acts not only as a conduit of nutrient and waste exchange between mother and developing fetus, but also functions as a regulator of the intrauterine environment. Recent work has identified changes in the expression of candidate genes, often through epigenetic alteration, which alter the placenta's function and impact fetal growth. In this study, we used the Illumina Infinium HumanMethylation27 BeadChip array to examine genome-wide DNA methylation patterns in 206 term human placentas. Semi-supervised recursively partitioned mixture modeling was implemented to identify specific patterns of placental DNA methylation that could differentially classify intrauterine growth restriction (IUGR) and small for gestational age (SGA) placentas from appropriate for gestational age (AGA) placentas, and these associations were validated in a masked testing series of samples. Our work demonstrates that patterns of DNA methylation in human placenta are reliably and significantly associated with infant growth and serve as a proof of principle that methylation status in the human term placenta can function as a marker for the intrauterine environment, and could potentially play a critical functional role in fetal development.

Download full-text

Full-text

Available from: Carolyn E Banister, Jul 01, 2015
1 Follower
 · 
159 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of genome-wide methylation arrays has proved very informative to investigate both clinical and biological questions in human epigenomics. The use of clustering methods either for exploration of these data or to compare to an a priori grouping, e.g., normal versus disease allows assessment of groupings of data without user bias. However no consensus on the methods to use for clustering of methylation array approaches has been reached. To determine the most appropriate clustering method for analysis of illumina array methylation data, a collection of data sets was simulated and used to compare clustering methods. Both hierarchical clustering and non-hierarchical clustering methods (k-means, k-medoids, and fuzzy clustering algorithms) were compared using a range of distance and linkage methods. As no single method consistently outperformed others across different simulations, we propose a method to capture the best clustering outcome based on an additional measure, the silhouette width. This approach produced a consistently higher cluster accuracy compared to using any one method in isolation.
    Frontiers in Genetics 12/2011; 2:88. DOI:10.3389/fgene.2011.00088
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fetal growth restriction (FGR) is a pathological condition that refers to a fetus that fails to reach his/her genetically predetermined growth potential. By epigenetic effects, substrate and energy deprivation in utero modify fetal metabolism with possible life-long impacts. Management of FGR still represents one of the main challenges for the obstetricians, both for the complexities of management of severe early FGR and for the diagnostic difficulties in late and term FGR. Late onset and term FGR define an intrauterine trajectory of growth that falls below its potential late in gestation, after 34 and 37 weeks of gestation, respectively. Ultrasound biometry examination is crucial for an accurate diagnosis of FGR. Pregnancies at risk of FGR should be considered for longitudinal ultrasound monitoring beyond the routine ultrasound screening at 20 weeks of gestation. Functional assessment of placental and fetal circulation by Doppler velocimetry and blood flow volume, together with computerized assessment of fetal heart rate variability, are key examinations in early and late FGR to assess severity of the disease and monitor fetal wellbeing. Appropriate timing of delivery in early FGR might change the outcome, and appropriate monitoring in late and term FGR might avoid unnecessary interventions.
    06/2013; 2(2). DOI:10.1007/s13669-013-0043-x
  • Source