Perinatal Exposure to Nicotine Alters Sperm RNA Profiles in Rats
FRONTIERS IN ENDOCRINOLOGY(2022)
Abstract
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 PPAR gamma agonist, can attenuate the effect of nicotine and reverse the sperm-borne RNA profiles of F1 male rats to close to placebo control levels.
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Key words
asthma, nicotine, smoking, lung, epigenetic inheritance, small RNA, large noncoding RNA
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