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Multiple Generation Distinct Toxicant Exposures Induce Epigenetic-Transgenerational-Inheritance of Enhanced Pathology and Obesity

ABSTRACT: This study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide DDT (dichlorodiphenyltrichloroethane) on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational-generation were examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions (DMRs) were observed. The F3-F5 generations were similar in approximately 50% of the DMRs. The pathology of each generation was assessed in the testis, ovary, kidney, prostate, obesity, and tumors. The pathology used a newly developed Deep Learning (DL), artificial intelligence (AI), based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Therefore, the multiple generational exposures, which occurs in human populations, may increase epigenetic impacts and disease susceptibility.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE244603 | GEO | 2024/12/02

REPOSITORIES: GEO

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