Epigenome-wide association study for pesticide (Permethrin and DEET) induced DNA methylation epimutation biomarkers for specific transgenerational disease.
Animals
Biomarkers
DEET
/ toxicity
DNA Methylation
Epigenesis, Genetic
Epigenome
Female
Insect Repellents
/ toxicity
Insecticides
/ toxicity
Kidney Diseases
/ chemically induced
Male
Maternal-Fetal Exchange
Permethrin
/ toxicity
Pregnancy
Prenatal Exposure Delayed Effects
Prostatic Diseases
/ chemically induced
Rats, Sprague-Dawley
Testicular Diseases
/ chemically induced
EWAS
Kidney
Multiple disease
N,N-diethyl-meta-toluamide
Pathology
Permethrin
Prostate
Sperm
Testis
Transgenerational
Journal
Environmental health : a global access science source
ISSN: 1476-069X
Titre abrégé: Environ Health
Pays: England
ID NLM: 101147645
Informations de publication
Date de publication:
04 11 2020
04 11 2020
Historique:
received:
01
07
2020
accepted:
14
10
2020
entrez:
5
11
2020
pubmed:
6
11
2020
medline:
18
2
2021
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Identifiants
pubmed: 33148267
doi: 10.1186/s12940-020-00666-y
pii: 10.1186/s12940-020-00666-y
pmc: PMC7643320
doi:
Substances chimiques
Biomarkers
0
Insect Repellents
0
Insecticides
0
DEET
134-62-3
Permethrin
509F88P9SZ
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
109Subventions
Organisme : John Templeton Foundation
ID : 50183
Pays : International
Organisme : John Templeton Foundation
ID : 61174
Pays : International
Organisme : NIH HHS
ID : ES012974
Pays : United States
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