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Transgenerational epigenetic and transcriptomic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rat [Bisulfite-Seq]

ABSTRACT: Transgenerational epigenetic and transcriptomic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rat [Bisulfite-Seq]

PROVIDER: PRJNA601972 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10908800.fastq.gz	Fastqsanger.gz
	SRR10908801.fastq.gz	Fastqsanger.gz
	SRR10908770.fastq.gz	Fastqsanger.gz
	SRR10908771.fastq.gz	Fastqsanger.gz
	SRR10908772.fastq.gz	Fastqsanger.gz

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Transgenerational epigenetic and transcriptomic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rat

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Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations

Project description:Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

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Project description:A toxicogenomics approach was used to qualitatively and quantitatively compare the gene expression changes in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Hepatocytes from five individual rats and five individual humans were exposed for 24 hours to 11 concentrations of TCDD ranging from 0.00001 nM to 100 nM and a vehicle control. Gene expression changes were analyzed using whole genome microarrays.

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