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Epigenome-wide association study for pesticide (Permethrin and DEET) induced DNA methylation epimutation biomarkers for specific transgenerational disease

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Title: Epigenome-wide association study for pesticide (Permethrin and DEET) induced DNA methylation epimutation biomarkers for specific transgenerational disease
Authors: Thorson, Jennifer L M, Beck, Daniel, Ben Maamar, Millissia, Nilsson, Eric E, Skinner, Michael K
Publication Year: 2020
Subject Terms: Epigenetics, Biomarkers, Pregnancy, DEET - toxicity, DNA Methylation, Epigenesis, Genetic, Epigenome, Insect Repellents - toxicity, Insecticides - toxicity, Kidney Diseases - chemically induced, Maternal-Fetal Exchange, Permethrin - toxicity, Prenatal Exposure Delayed Effects, Prostatic Diseases - chemically induced, Rats, Sprague-Dawley, Testicular Diseases - chemically induced
Description: Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The current study was designed as an epigenome-wide association study (EWAS) to identify potential sperm DNA methylation epimutation biomarkers for specific transgenerational disease. ; Outbred Sprague Dawley gestating female rats (F0) were transiently exposed during fetal gonadal sex determination to the pesticide combination including Permethrin and DEET. The F3 generation great-grand offspring within the pesticide lineage were aged to 1 year. The transgenerational adult male rat sperm were collected from individuals with single and multiple diseases and compared to non-diseased animals to identify differential DNA methylation regions (DMRs) as biomarkers for specific transgenerational disease. ; The exposure of gestating female rats to a permethrin and DEET pesticide combination promoted transgenerational testis disease, prostate disease, kidney disease, and the presence of multiple disease in the subsequent F3 generation great-grand offspring. The disease DMRs were found to be disease specific with negligible overlap between different diseases. The genomic features of CpG density, DMR length, and chromosomal locations of the disease specific DMRs were investigated. Interestingly, the majority of the disease specific sperm DMR associated genes have been previously found to be linked to relevant disease specific genes. ; Observations demonstrate the EWAS approach identified disease specific biomarkers that can be potentially used to assess transgenerational disease susceptibility and facilitate the clinical management of environmentally induced pathology.
Document Type: article in journal/newspaper
File Description: pdf
Language: English
Relation: ispartof: Environmental health spage 109 epage 109 issue 1 vol 19; PMC7643320; WOS:000585871800001; 99901080303801842; https://rex.libraries.wsu.edu/view/delivery/01ALLIANCE_WSU/12406255000001842/13406177300001842; alma:01ALLIANCE_WSU/bibs/99901080303801842
DOI: 10.1186/s12940-020-00666-y
Availability: https://doi.org/10.1186/s12940-020-00666-y
https://rex.libraries.wsu.edu/esploro/outputs/journalArticle/Epigenome-wide-association-study-for-pesticide-Permethrin/99901080303801842
https://rex.libraries.wsu.edu/view/delivery/01ALLIANCE_WSU/12406255000001842/13406177300001842
Rights: Open ; CC BY V4.0
Accession Number: edsbas.DD254BD8
Database: BASE
Description
Abstract:Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The current study was designed as an epigenome-wide association study (EWAS) to identify potential sperm DNA methylation epimutation biomarkers for specific transgenerational disease. ; Outbred Sprague Dawley gestating female rats (F0) were transiently exposed during fetal gonadal sex determination to the pesticide combination including Permethrin and DEET. The F3 generation great-grand offspring within the pesticide lineage were aged to 1 year. The transgenerational adult male rat sperm were collected from individuals with single and multiple diseases and compared to non-diseased animals to identify differential DNA methylation regions (DMRs) as biomarkers for specific transgenerational disease. ; The exposure of gestating female rats to a permethrin and DEET pesticide combination promoted transgenerational testis disease, prostate disease, kidney disease, and the presence of multiple disease in the subsequent F3 generation great-grand offspring. The disease DMRs were found to be disease specific with negligible overlap between different diseases. The genomic features of CpG density, DMR length, and chromosomal locations of the disease specific DMRs were investigated. Interestingly, the majority of the disease specific sperm DMR associated genes have been previously found to be linked to relevant disease specific genes. ; Observations demonstrate the EWAS approach identified disease specific biomarkers that can be potentially used to assess transgenerational disease susceptibility and facilitate the clinical management of environmentally induced pathology.
DOI:10.1186/s12940-020-00666-y