DataSheet_6_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密切相关，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。尤为值得关注的是，该疾病表型具有可遗传性：即便后续世代不再持续暴露于吸烟环境，哮喘仍可跨多代延续。尽管围产期吸烟或尼古丁暴露所诱导的儿童哮喘，其分子机制仍不明晰，但已有表观遗传机制假说被提出，且该假说得到了我们此前针对生殖系DNA甲基化（5mC）与组蛋白标记（H3与H4乙酰化）的分析数据的支持。为进一步探究围产期尼古丁暴露诱导的儿童哮喘的潜在表观遗传传递特性，我们对F1代雄性大鼠精子中的大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谱（包括信使RNA[mRNA]与小RNA）；而PPARγ激动剂罗格列酮（rosiglitazone）可减弱尼古丁的上述调控作用，并将F1代雄性大鼠的精子RNA谱逆转至接近安慰剂对照组的水平。