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

Autor: Michael K. Skinner, Eric E. Nilsson, Millissia Ben Maamar, Jennifer L M Thorson, Daniel Beck
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Insecticides
Prostatic Diseases
Health
Toxicology and Mutagenesis
Disease
Kidney
Multiple disease
Epigenesis
Genetic
Rats
Sprague-Dawley
Epigenome
0302 clinical medicine
Pregnancy
Testis
Pathology
Maternal-Fetal Exchange
Genetics
lcsh:Public aspects of medicine
Prostate
Methylation
CpG site
Prenatal Exposure Delayed Effects
DNA methylation
lcsh:Industrial medicine. Industrial hygiene
Female
Kidney Diseases
Transgenerational
medicine.drug
Offspring
DEET
Biology
Testicular Diseases
lcsh:RC963-969
03 medical and health sciences
medicine
Animals
Epigenetics
Permethrin
EWAS
Research
Public Health
Environmental and Occupational Health
lcsh:RA1-1270
DNA Methylation
N
N-diethyl-meta-toluamide
Sperm
030104 developmental biology
Insect Repellents
030217 neurology & neurosurgery
Biomarkers
Zdroj: Environmental Health
Environmental Health, Vol 19, Iss 1, Pp 1-17 (2020)
ISSN: 1476-069X
Popis: BackgroundPermethrin 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.MethodsOutbred 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.ResultsThe 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.ConclusionsObservations 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.
Databáze: OpenAIRE
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