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.已有研究证实，环境化合物可诱导疾病的表观遗传跨代遗传。本研究旨在探究含喷气燃料（JP-8）的烃类混合物是否会引发疾病的表观遗传跨代遗传。实验中，我们在胎儿性腺发育阶段，对妊娠的F0代雌性大鼠进行了短暂暴露处理。直接暴露的F1代个体出现多种病症：雌雄个体肾脏异常发生率均升高；雄性个体还伴随前列腺异常与青春期发育异常；雌性个体则出现原始卵泡丢失与多囊卵巢疾病。首个跨代子代群体为F3代，喷气燃料暴露谱系的F3代个体中，雌性个体原始卵泡丢失与多囊卵巢疾病的发生率升高，雌雄个体均出现肥胖症状。对该谱系F3代个体的精子表观组进行分析后，共鉴定出33个差异DNA甲基化区域，即表观突变（epimutations）。本研究结果表明，烃类化合物可诱导疾病与精子表观突变的表观遗传跨代遗传，而精子表观突变可作为祖先环境暴露的潜在生物标志物。