DataSheet_8_Perinatal Exposure to Nicotine Alters Sperm RNA Profiles in Rats.xlsx

Perinatal exposure to smoking has been associated with childhood asthma, one of the most common pediatric conditions affecting millions of children globally. Of great interest, this disease phenotype appears heritable as it can persist across multiple generations even in the absence of persistent exposure to smoking in subsequent generations. Although the molecular mechanisms underlying childhood asthma induced by perinatal exposure to smoking or nicotine remain elusive, an epigenetic mechanism has been proposed, which is supported by the data from our earlier analyses on germline DNA methylation (5mC) and histone marks (H3 and H4 acetylation). To further investigate the potential epigenetic inheritance of childhood asthma induced by perinatal nicotine exposure, we profiled both large and small RNAs in the sperm of F1 male rats. Our data revealed that perinatal exposure to nicotine leads to alterations in the profiles of sperm-borne RNAs, including mRNAs and small RNAs, and that rosiglitazone, a PPARγ agonist, can attenuate the effect of nicotine and reverse the sperm-borne RNA profiles of F1 male rats to close to placebo control levels.

围产期吸烟暴露与儿童哮喘存在关联，儿童哮喘是全球范围内影响数百万儿童的最常见儿科疾病之一。值得关注的是，该疾病表型呈现可遗传性：即使后续世代不再持续接触烟草烟雾，其仍可跨多代传递。尽管围产期吸烟或尼古丁暴露诱发儿童哮喘的分子机制尚不明晰，但已有表观遗传机制假说被提出，该假说得到了我们早期针对生殖系DNA甲基化（5mC）与组蛋白修饰（H3、H4乙酰化）的分析数据支持。为进一步探究围产期尼古丁暴露诱发儿童哮喘的潜在表观遗传传递效应，我们对F1代雄性大鼠精子中的长链RNA与小RNA进行了表达谱分析。本研究数据显示，围产期尼古丁暴露会改变精子携带的RNA（包括信使RNA与小RNA）的表达谱；而PPARγ激动剂罗格列酮可削弱尼古丁的上述效应，将F1代雄性大鼠的精子RNA表达谱逆转至接近安慰剂对照组的水平。