Epigenome-wide association study for atrazine induced transgenerational DNA methylation and histone retention sperm epigenetic biomarkers for disease

Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential DNA...

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Bibliographic Details
Published in:PloS one 2020-12, Vol.15 (12), p.e0239380
Main Authors: Thorson, Jennifer L M, Beck, Daniel, Ben Maamar, Millissia, Nilsson, Eric E, McBirney, Margaux, Skinner, Michael K
Format: Article
Language:English
Subjects:
Agrochemicals
Animals
Atrazine
Atrazine - adverse effects
Biological markers
Biology
Biology and Life Sciences
Biomarkers
Biomarkers - metabolism
Chromatin
Complications and side effects
Deoxyribonucleic acid
Disease
Disease - genetics
Disease Susceptibility
DNA
DNA methylation
DNA Methylation - drug effects
DNA Methylation - genetics
DNA sequencing
Drinking water
Embryos
Epigenesis, Genetic - drug effects
Epigenesis, Genetic - genetics
Epigenetic inheritance
Epigenetics
Epigenome - genetics
Epigenomics - methods
Female
Females
Gene sequencing
Generations
Genetic aspects
Genetic Predisposition to Disease - genetics
Genetic research
Genetic susceptibility
Genomes
Health aspects
Herbicides
Herbicides - pharmacology
Heredity
Heredity - drug effects
Heredity - genetics
Histones
Histones - genetics
Histones - metabolism
Immunoprecipitation
Infertility
Kidney diseases
Male
Males
Medicine and Health Sciences
Methylation
Motility
Pathology
Physical Sciences
Prostate
Proteins
Puberty
Rats
Rats, Sprague-Dawley
Research and Analysis Methods
Retention
Sex determination
Sperm
Spermatozoa
Spermatozoa - drug effects
Spermatozoa - metabolism
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Summary:Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential DNA methylation regions (DMRs) and differential histone retention regions (DHRs). Gestating female F0 generation rats were transiently exposed to atrazine during the period of embryonic gonadal sex determination, and then subsequent F1, F2, and F3 generations obtained in the absence of any continued exposure. The transgenerational F3 generation males were assessed for disease and sperm collected for epigenetic analysis. Pathology was observed in pubertal onset and for testis disease, prostate disease, kidney disease, lean pathology, and multiple disease. For these pathologies, sufficient numbers of individual males with only a single specific disease were identified. The sperm DNA and chromatin were isolated from adult one-year animals with the specific diseases and analyzed for DMRs with methylated DNA immunoprecipitation (MeDIP) sequencing and DHRs with histone chromatin immunoprecipitation (ChIP) sequencing. Transgenerational F3 generation males with or without disease were compared to identify the disease specific epimutation biomarkers. All pathologies were found to have disease specific DMRs and DHRs which were found to predominantly be distinct for each disease. No common DMRs or DHRs were found among all the pathologies. Epimutation gene associations were identified and found to correlate to previously known disease linked genes. This is one of the first observations of potential sperm disease biomarkers for histone retention sites. Although further studies with expanded animal numbers are required, the current study provides evidence the EWAS analysis is effective for the identification of potential pathology epimutation biomarkers for disease susceptibility.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0239380