Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

Environmental compounds have been shown to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a hydrocarbon mixture involving jet fuel (JP-8) promotes epigenetic transgenerational inheritance of disease. Gestating F0 generation female rats were transiently exposed during the fetal gonadal development period. The direct exposure F1 generation had an increased incidence of kidney abnormalities in both females and males, prostate and pubertal abnormalities in males, and primordial follicle loss and polycystic ovarian disease in females. The first transgenerational generation is the F3 generation, and the jet fuel lineage had an increased incidence of primordial follicle loss and polycystic ovarian disease in females, and obesity in both females and males. Analysis of the jet fuel lineage F3 generation sperm epigenome identified 33 differential DNA methylation regions, termed epimutations. Observations demonstrate hydrocarbons can promote epigenetic transgenerational inheritance of disease and sperm epimutations, potential biomarkers for ancestral exposures.

Tracey R ，Manikkam M ，Guerrero-Bosagna C ，Skinner MK ... -  《-》

Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline.

Manikkam M ，Haque MM ，Guerrero-Bosagna C ，Nilsson EE ，Skinner MK ... -  《PLoS One》

Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations.

Manikkam M ，Tracey R ，Guerrero-Bosagna C ，Skinner MK ... -  《PLoS One》

Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

Manikkam M ，Tracey R ，Guerrero-Bosagna C ，Skinner MK ... -  《PLoS One》

Epigenome-wide association study for transgenerational disease sperm epimutation biomarkers following ancestral exposure to jet fuel hydrocarbons.

Jet fuel hydrocarbons is the generic name for aviation fuels used in gas-turbine engine powered aircraft. The Deepwater Horizon oil rig explosion created the largest environmental disaster in U.S. history, and the second largest oil spill in human history with over 800 million liters of hydrocarbons released into the Gulf of Mexico over a period of 3 months. Due to the widespread use of jet fuel hydrocarbons, this compound mixture has been recognized as the single largest chemical exposure for military personnel. Previous animal studies have demonstrated the ability of jet fuel (JP-8) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The diseases observed include late puberty, kidney, obesity and multiple disease pathologies. The current study is distinct and was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations show disease specific differential DNA methylation regions (DMRs) called epimutations in the transgenerational F3 generation great-grand-offspring male rats ancestrally exposed to jet fuel. The potential epigenetic DMR biomarkers were identified for late puberty, kidney, obesity, and multiple diseases, and found to be predominantly disease specific. These disease specific DMRs have associated genes that were previously shown to be linked with each of these specific diseases. Therefore, the germline (i.e. sperm) has environmentally induced ancestrally derived epimutations that have the potential to transgenerationally transmit disease susceptibilities to subsequent generations. Epigenetic biomarkers for specific diseases could be developed as medical diagnostics to facilitate clinical management of disease, and allow preventative medicine therapeutics.

Ben Maamar M ，Nilsson E ，Thorson JLM ，Beck D ，Skinner MK ... -  《-》