Perinatal nicotine exposure-induced transgenerational asthma: Effects of reexposure in F1 gestation.
Perinatal nicotine exposure-induced transgenerational asthma: Effects of reexposure in F1 gestation.
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DOI：
10.1096/fj.201902386r
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
Rehan VK
中科院分区：
文献类型：
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作者：
Liu J;Yu C;Doherty TM;Akbari O;Allard P;Rehan VK
在大鼠模型中，围产期尼古丁暴露导致表观遗传驱动的多代和跨代传播性哮喘表型，这种表型倾向于随着世代的推移而减弱。然而，在F1(子代1)妊娠期重复尼古丁暴露对传播表型的影响尚不清楚。使用已建立的大鼠模型，我们以性别特异性的方式比较了仅在F0孕期、在F0和F1(F0/F1)孕期以及在两组都没有(对照组)围产期接触尼古丁后，F2后代的肺功能、呼吸道间充质反应性标志物和全局性腺DNA甲基化的变化。仅F0和F0/F1暴露组都表现出哮喘表型，这种影响在F0/F1暴露组更明显，特别是在男性。F0/F1暴露组大鼠睾丸DNA甲基化增加，卵巢DNA甲基化减少。由于吸烟者的后代比不吸烟者的后代更有可能吸烟，如果母亲和祖母在怀孕期间都吸烟，这就为更严重的哮喘奠定了基础。在F1代中，尼古丁重新暴露后性腺DNA甲基化变化增加，这表明表观遗传机制可能是后天获得性表型性状，特别是尼古丁诱导的哮喘的跨代遗传的基础。
In a rat model, perinatal nicotine exposure results in an epigenetically driven multi-and trans-generationally transmitted asthmatic phenotype that tends to wane over successive generations. However, the effect of repeat nicotine exposure during the F1 (Filial 1) gestational period on the transmitted phenotype is unknown. Using a well-established rat model, we compared lung function, mesenchymal markers of airway reactivity, and global gonadal DNA methylation changes in F2 offspring in a sex-specific manner following perinatal exposure to nicotine in only the F0 gestation, in both F0 and F1 (F0/F1) gestations, and in neither (control group). Both F0 only and F0/F1 exposure groups showed an asthmatic phenotype, an effect that was more pronounced in the F0/F1 exposure group, especially in males. Testicular global DNA methylation increased, while ovarian global DNA methylation decreased in the F0/F1 exposed group. Since the offspring of smokers are more likely to smoke than the offspring of nonsmokers, this sets the stage for more severe asthma if both mother and grandmother had smoked during their pregnancies. Increased gonadal DNA methylation changes following nicotine reexposure in the F1 generation suggests that epigenetic mechanisms might well underlie the transgenerational inheritance of acquired phenotypic traits in general and nicotine-induced asthma in particular.