Gestation‐dependent changes in human placental global DNA methylation levels

Chavan‐Gautam, Preeti; Sundrani, Deepali; Pisal, Hemlata; Nimbargi, Vandana; Mehendale, Savita; Joshi, Sadhana

doi:10.1002/mrd.21296

Cited by 49 publications

(36 citation statements)

References 3 publications

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“…This was a cross-sectional design in which 76 women delivering at term (control group), 67 women delivering preterm (PT group) and 49 women with preeclampsia delivering preterm (PT-PE group) with singleton pregnancy were recruited. The inclusion and exclusion criteria were as described in our earlier studies [9,10,11]. Briefly, women were excluded from the study if there was evidence of other pregnancy complications, alcohol or drug abuse.…”

Section: Methodsmentioning

confidence: 99%

“…We recently reported increased homocysteine concentrations and altered placental global methylation levels in women with pregnancy complications such as preeclampsia and preterm delivery [9,10,11]. The observed abnormal global DNA methylation may reflect alterations in the normal temporal regulation of gene expression that is crucial for the optimal development of the fetus and may have implications for metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Reduced Folate, Increased Vitamin B<sub>12</sub> and Homocysteine Concentrations in Women Delivering Preterm

et al. 2012

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Background and Aim: Maternal nutrition is an important determinant of the duration of pregnancy and fetal growth, and thereby influences pregnancy outcome. Folic acid and vitamin B₁₂ are involved in one-carbon metabolism and are reported to underlie intrauterine programming of adult diseases. Methods: In the present study, the levels of folate, vitamin B₁₂ and homocysteine were measured in mothers delivering preterm (PT; gestation <37 weeks; n = 67), those delivering preterm due to preeclampsia (PT-PE; n = 49) and women delivering at term (control group; n = 76). Results: Increased vitamin B₁₂ and homocysteine levels (p < 0.05 for both) were seen in the PT-PE and PT groups as compared to the controls. In addition, reduced folate levels (p < 0.05) were observed in the PT group. A negative association of maternal plasma homocysteine with birth weight was seen in the idiopathic preterm group. Conclusions: Altered maternal micronutrients and resultant increased homocysteine concentrations exist in women delivering preterm. These alterations may also be partly associated with other factors such as undiagnosed inflammatory conditions or inadequate placentation in some women. Since these micronutrients play an important role in epigenetic regulation of vital genes involved in the fetal programming of adult diseases, further studies need to be undertaken to understand their role in preterm deliveries.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reduced Folate, Increased Vitamin B<sub>12</sub> and Homocysteine Concentrations in Women Delivering Preterm

et al. 2012

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“…In addition, Chu et al (15) found large regions of hypomethylation in placenta compared with maternal blood cells; however, the analysis was limited to chromosomes 13,18, and 21. Further study of DNA methylation in placenta is warranted because changes in placental methylation have been associated with infant growth rate, pre-eclampsia, and preterm delivery (17)(18)(19)(20)(21). Furthermore, the placenta is the key mediator of environmental exposures affecting developmental programming of the fetus, which can have long-lasting effects on health (22).…”

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confidence: 99%

The human placenta methylome

Schroeder

Blair

Lott

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Tissue-specific DNA methylation is found at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). Recently, sequencing of bisulfite-treated DNA (MethylCseq) has revealed large partially methylated domains (PMDs) in some human cell lines. PMDs cover up to 40% of the genome and are associated with gene repression and inactive chromatin marks. However, to date, only cultured cells and cancers have shown evidence for PMDs. Here, we performed MethylC-seq in full-term human placenta and demonstrate it is the first known normal tissue showing clear evidence of PMDs. We found that PMDs cover 37% of the placental genome, are stable throughout gestation and between individuals, and can be observed with lower sensitivity in Illumina 450K Infinium data. RNA-seq analysis confirmed that genes in PMDs are repressed in placenta. Using a hidden Markov model to map placental PMDs genome-wide and compare them to PMDs in other cell lines, we found that genes within placental PMDs have tissuespecific functions. For regulatory regions, methylation levels in promoter CpG islands are actually higher for genes within placental PMDs, despite the lower overall methylation of surrounding regions. Similar to PMDs, polycomb-regulated regions are hypomethylated but smaller and distinct from PMDs, with some being hypermethylated in placenta compared with other tissues. These results suggest that PMDs are a developmentally dynamic feature of the methylome that are relevant for understanding both normal development and cancer and may be of use as epigenetic biomarkers.epigenomics | hypomethylation

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“…On a global level, placental tissues are hypomethylated compared with most somatic tissues (5,6 ). At the gene level, the methylation status of particular genomic loci is a specific signature of placental tissues (6,7 ), and this signature shows gestational age-dependent changes (8 ). Imprinted genes, namely genes for which expression is dependent on the parental origin of alleles, serve key functions in the placenta (9 ).…”

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confidence: 99%