Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Placental methylation profile in women exposed to fluoride and its association with kidney volume at birth

ABSTRACT: This experiment investigates the relationship between maternal fluoride exposure during pregnancy and DNA methylation patterns in the placenta, aiming to identify epigenetic alterations associated with reduced kidney volume at birth. Placental samples were collected from term deliveries and classified according to maternal fluoride concentration and neonatal kidney volume. Genomic DNA was extracted, bisulfite-converted, and hybridized to the Illumina Infinium MethylationEPIC v2.0 BeadChip to quantify methylation across more than 935,000 CpG sites. Data preprocessing, quality control, and normalization were performed using the SeSAMe package in R, following Illumina’s recommended pipeline for EPIC v2.0 arrays. Differentially methylated positions and regions were identified to explore potential epigenetic mechanisms linking prenatal fluoride exposure with altered renal development.

ORGANISM(S): Homo sapiens

SUBMITTER: Leslie Zúñiga Macías

PROVIDER: E-MTAB-16226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. The initial lesion is believed to be the relatively benign precursor lesion (ICGNU), from which either highly chemosensitive seminomas or the more aggressive non-seminomas develop. Previous analyses of selected genes have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. However, the genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumoursâ biology have not yet been established. Here genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data. This demonstrated that the seminoma cells exhibited very little aberrant DNA methylation while non-seminoma cells exhibited very high levels of DNA methylation. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested did indeed play a role in their silencing and many of these genes were also differentially expressed in primary tumours. Through this approach the genes silenced in the various GCT cell lines were identified. Conclusions: Several pluripotency-associated genes, never before implicated in this type of cancer, were identified as a major functional group of silenced genes. Silencing of these factors that normally suppress somatic differentiation might play an important role in the progression to non-seminoma formation. Genomic DNA and RNA was extracted from cell lines representing four subtypes of GCT. RNA was subjected to Affymetric expression array analysis while DNA was bisulfite treated and analysed using Illumina Infinium 450K arrays. Statistical approaches were used to correlate methylation and expression for each gene.

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Placental methylation profile in women exposed to fluoride and its association with kidney volume at birth

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