Nicotine exposure and transgenerational impact: a prospective study on small regulatory microRNAs

Abstract

Early developmental stages are highly sensitive to stress and it has been reported that pre-conditioning with tobacco smoking during adolescence predisposes those youngsters to become smokers as adults. However, the molecular mechanisms of nicotine-induced transgenerational consequences are unknown. In this study, we genome-widely investigated the impact of nicotine exposure on small regulatory microRNAs (miRNAs) and its implication on health disorders at a transgenerational aspect. Our results demonstrate that nicotine exposure, even at the low dose, affected the global expression profiles of miRNAs not only in the treated worms (F0 parent generation) but also in two subsequent generations (F1 and F2, children and grandchildren). Some miRNAs were commonly affected by nicotine across two or more generations while others were specific to one. The general miRNA patterns followed a “two-hit” model as a function of nicotine exposure and abstinence. Target prediction and pathway enrichment analyses showed daf-4, daf-1, fos-1, cmk-1, and unc-30 to be potential effectors of nicotine addiction. These genes are involved in physiological states and phenotypes that paralleled previously published nicotine induced behavior. Our study offered new insights and further awareness on the transgenerational effects of nicotine exposed during the vulnerable post-embryonic stages, and identified new biomarkers for nicotine addiction.

Prevalência e fatores associados ao tabagismo em fumicultores do Sul do Brasil

“…A alta prevalência de tabagismo entre homens fumicultores sugere que o trabalho direto com o tabaco estimula o consumo do produto, para além do que acontece com os demais agricultores. Estudos recentes explicam o papel da transmissão familiar e epigenética no uso e dependência de substâncias e na manutenção de comportamentos específicos através das gerações 14,15,16 . Dessa forma, fumicultores estariam expostos à nicotina desde a vida embrionária, receberiam a herança epigenética de seus progenitores expostos à nicotina e cresceriam em um cluster familiar de adicção ao tabaco e ao álcool.…”

Involvement of Neurotransmitter and Nrf2 in Nicotine- and Cigarette Smoke-Induced Testicular Toxicity in Adult Rats

“…39 Serum cotinine is not detected in the control animals due to the nonavailability of the substance in the serum throughout the study period, suggesting toxic impact of the studied doses upon exposure, which corroborates several previous observations. 13,18,19,48,49 Moreover, Seccareccia et al 51 reported the positive association between self-reported nicotine exposure and serum cotinine levels among the smokers, nonsmokers reporting exposure to environmental tobacco smoke (ETS), and nonsmokers with no ETS exposure even after the adjustment of age and sociodemographic and behavioral factors. Nicotine exposure from the passive tobacco smoke can also endanger plasma nicotine concentration equivalent to the levels produced by the tobacco smoking and are associated Table 2.…”

“…Our results are in corroboration with the several previous observations showing psychostimulant or drug abuse that can induce germinal cell loss including SC and spermatids, resulting in disruption of spermatogenesis. [17][18][19]53,54 Rajpurkar et al 55 claimed that CS reduces the number of germial cells, height of germinal epithelium, tubular diameter and induces apoptosis in the testis due to the presence of many toxic substances in cigarettes. 56 However, Leydig cell histology that remains unaltered upon exposure in the present study may indicate that the current doses may not be able to initiate any change in the testicular steroidogenic process; the discrepancy of which with the previous reports 57,58 may be due to the differences in the experimental design, species, strains, etc.…”

“…and exerts negative impact on sperm production and male fertility, and behavioral disorders. 13,14,[16][17][18][19] Testosterone, on the other hand, regulates cognitive behavior by modulating brain circuits and neuronal maturation involving DAergic midbrain reward system that originate in VTA, project to nucleus accumbens (NAcc), amygdale, hippocampus, and cerebral cortex. 27 Thus, in NAcc and striatum, the reinforcing effect of nicotine and other psychostimulants is characterized by increasing DA transmission that binds to the DA Rs, which can further induce DA R downregulation.…”

“…15 Nicotine/CS induces abnormal testis morphology and antioxidant depletion, and exerts negative impact on sperm production and fertility, 16,17 epigenetic changes, and behavioral as well as cogni-tive disorders. 18,19 Although testicular binding sites for nicotine/CS have been demonstrated, 20,21 the NT mechanism underlying nicotine/CS-induced testicular pathology is not fully reported.…”