Single-cell RNA sequencing of nicotine-exposed testes reveals differences in cell proportion and transcription
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE283769 | GEO | 2025/04/30
REPOSITORIES: GEO
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Project description:DNA methylation, a pivotal epigenetic modification, regulates the expression of numerous genes during spermatogenesis and influences health outcomes in offspring. We have conducted whole genome bisulfite sequencing (WGBS) to explore the effects of nicotine exposure on global sperm DNA methylation patterns. Previous studies have shown that nicotine exposure increased DNA methylation status in sperm, whereas the detailed mapping of global DNA methylation patterns remains elusive. In addition, whether the DNA methylation changes induced by nicotine may be reversible upon cessation is still unclear. Here, we demonstrated the effects of nicotine exposure on global sperm DNA methylation patterns and verified the reversibility of this phenomenon, providing new insights into the mechanisms by which smoking affects male fertility and the long-term health of offspring.
2025-04-30 | GSE284004 | GEO
Project description:Nicotine intake, whether through tobacco smoking or e-cigarettes, remains a global health concern. An emerging preclinical literature indicates that parental nicotine exposure produces behavioral, physiological, and molecular changes in subsequent generations. However, the heritable effects of voluntary parental nicotine taking are unknown. Here, we show increased acquisition of nicotine taking in male and female offspring of sires that self-administered nicotine. In contrast, self-administration of sucrose and cocaine were unaltered in male and female offspring suggesting that the intergenerational effects of paternal nicotine taking may be reinforcer specific. Further characterization revealed memory deficits and increased anxiety-like behaviors in drug-naïve male, but not female, offspring of nicotine-experienced sires. Using an unbiased, genome-wide approach, we discovered that these phenotypes were associated with decreased expression of Satb2, a transcription factor known to play important roles in synaptic plasticity and memory formation, in the hippocampus of nicotine-sired male offspring. This effect was sex-specific as no changes in Satb2 expression were found in nicotine-sired female offspring. Finally, increasing Satb2 levels in the hippocampus prevented the escalation of nicotine intake and rescued the memory deficits associated with paternal nicotine taking in male offspring. Collectively, these findings indicate that paternal nicotine taking produces heritable sex-specific molecular changes that promote addiction-like phenotypes and memory impairments in male offspring. To characterize the molecular changes associated with the heritable effects of paternal nicotine taking, an unbiased, whole-genome analysis was used to characterize the hippocampal transcriptome of drug-naïve F1 males
2022-04-01 | GSE199661 | GEO
Project description:Single-cell RNA sequencing of nicotine-exposed testes reveals differences in cell proportion and transcription
| PRJNA1195558 | ENA
Project description:Nicotine and cigarette smoking have been previously shown to inhibit the differentiation potential and miRNA expression of human periodontal ligament derived stem cells (PDLSCs). Electronic cigarette (EC) vapor also contains nicotine, as well as other non-nicotine compounds, and, like cigarette smoking, EC vaping results in similar routes of toxic exposure for PDLSCs. The effect of exposure on PDLSC miRNA expression is unknown. To determine these effects, cultured PDLSCs were exposed to media supplemented with 1 uM nicotine EC vapor extract for 72h, during which media was changed every 24h. To produce vapor extract, an EC filled with 36 mg/ml nicotine, 50%/50% (w/v) PG/VG, non-flavored e-liquid (American E-liquid) was vaped using an automated vaping robot programmed with experienced e-cigarette user patterns (i.e. puff volume: 70 ml, duration: 3s, frequency: 20s) and resulting vapor was extracted via a liquid impinger. 1 uM of pure (-)-nicotine liquid (Sigma Aldrich) was used as a positive control. Total miRNA was collected with the mirVana miRNA isolation kit. miRNA concentration and quality was measured by spectrophotometry and expression was analyzed with Affymetrix GeneChip miRNA 4.0 Arrays. Results were normalized against human-positive and negative chip controls using Robust Multi-Array Average Normalization.
2019-09-30 | E-MTAB-7893 | biostudies-arrayexpress
Project description:Cigarette smoking is associated with reduced risk of developing Parkinson’s disease (PD). To identify genes that interact with nicotine/smoking, we performed hypothesis-free genome-wide experiments in a paraquat-induced Drosophila model and in a case-control study of PD. We demonstrated that nicotine extends life-span in paraquat-treated Drosophila (P=4E-30). Brain tissue from flies treated with combinations of paraquat and nicotine revealed elevated expression of CG14691 with paraquat which was restored with nicotine co-treatment (P(interaction)=2E-11, P(FDR-adjusted)=4E-7). Independently, variants in the 5’ region of SV2C, a human ortholog of CG14691, gave the strongest signal for interaction with smoking (P(interaction)=9E-8). The effect of smoking on PD risk varied six-fold by SV2C genotype (P(heterogeneity)=4E-10). Moreover, SV2C variants identified here were associated with SVC2 gene-expression in the HapMap data. Present results suggest synaptic vesicle protein SV2C plays a role in PD pathogenesis, and that the SV2C genotype may be useful for clinical trials of nicotine for treating PD. Drosophila female heads were dissected after exposure to plain food, food with paraquat, food with nicotine, or food with both paraquat and nicotine, and genome-wide expression was quantified using Affymetrix microarrays. 20 heads were pooled per replicate, with each treatment in triplicate, and all flies were dissected at the same timepoint, after 10 days of pretreatment (with 0.1 mg/ml nicotine or no nicotine, depending on treatment group), and then a further 6 days of treatment with either 5 mM paraquat or no paraquat, continuing on the pretreatment dose of nicotine. One biological replicate in the paraquat-only group showed RNA degradation and was not included in the normalization or subsequent analyses.
2012-09-05 | E-GEOD-35930 | biostudies-arrayexpress
Project description:The Nicotine Metabolic Ratio (NMR), the ratio of two stable metabolites of nicotine, cotinine and trans-3’hydroxycotinin, is a determinant of the number of cigarettes smoked per day (CPD), of smoking topography, responsiveness to treatment via transdermal nicotine for smoking cessation, and carcinogen activation and level. The predominant gene involved in nicotine metabolism is CYP2A6, a highly polymorphic locus located in a cluster of P450 cytochrome protein loci on chr19q13. A recent study comprehensively modeling CYP2A6 genetic variation at seven polymorphisms and a related Nicotine Metabolic Ratio, the cotinine: cotinine+nicotine ratio, explains 72% of NMRC/C+N variation. These results suggest that additional genes may be contributing to nicotine and cotinine metabolism directly or via interaction with CYP2A6 or other genes. To identify additional genes that may influence the NMR, we conducted a genome-wide gene expression analysis of lymphoblastoid cell line (LCL) gene expression in a sample of monozygotic twins discordant for the NMR.
2015-09-30 | GSE51284 | GEO
Project description:Although it is increasingly accepted that some paternal environmental conditions can influence phenotypes in future generations, it remains unclear whether phenotypes induced in offspring represent specific responses to particular aspects of the paternal exposure history, or whether they represent a more generic response to paternal “quality of life”. To establish a paternal effect model based on a specific ligand-receptor interaction and thereby enable pharmacological interrogation of the offspring phenotype, we explored the effects of paternal nicotine administration on offspring phenotype in mouse. We show that paternal exposure to chronic nicotine induced a broad protective response to xenobiotic exposure in the next generation. This effect manifested as increased survival following an injection of toxic levels of nicotine, was specific to male offspring, and was only observed after these offspring were first acclimated to low levels of nicotine for a week. Importantly, offspring xenobiotic resistance was documented not only for toxic nicotine challenge, but also for toxic cocaine challenge, indicating that paternal nicotine exposure reprograms offspring to become broadly resistant to environmental toxins. Mechanistically, the reprogrammed state was characterized by enhanced clearance of nicotine in drug-acclimated animals, and we found that isolated hepatocytes displayed upregulation of enzymes that metabolize xenobiotics. Taken together, our data show that paternal nicotine exposure induces a protective phenotype in offspring by enhancing metabolic tolerance to xenobiotics in the environment.
2017-02-02 | GSE92240 | GEO
Project description:Spermiogenesis in Drosophila melanogaster is a highly conserved process and essential for male fertility. In this haploid phase of spermatogenesis, motile sperm are assembled from round cells, flagella are assembled, and needle-shaped nuclei with highly compacted genomes are formed. We aimed at identifying proteins relevant for the maturation phase from spermatids to sperm. As transcription takes place mainly in spermatocytes, and transcripts with relevance for post-meiotic sperm development are translationally repressed for days, we comparatively analysed the prote-ome of larval testes (stages before meiotic divisions), of testes of 1–2-day-old pupae (meiotic and early spermatid stages) and adult flies (late spermatids and sperm). We identified 6677 pro-teins, with 422 solely detected in larval testes, 623 in pupal testes and 634 in adult testes. We analysed a few so far uncharacterized proteins with repect to stage specific expression and im-portance for male fertility. For example, Mst84B (gene CG1988), a very basic cysteine- and lysine-rich nuclear protein, was present in the phase of transition from a histone-based to a pro-tamine-based chromatin structure. CG6332 encodes d-Theg, which is related to the mouse tHEG and human THEG proteins. Mutants of d-Theg lacked sperm in the seminal vesicles and were sterile. The identification of numerous predicted proteins underscores the high potential of pro-teome analysis for future analyses of spermatogenesis.
2019-02-01 | PXD010627 | Pride
Project description:Cigarette smoking is associated with reduced risk of developing Parkinson’s disease (PD). To identify genes that interact with nicotine/smoking, we performed hypothesis-free genome-wide experiments in a paraquat-induced Drosophila model and in a case-control study of PD. We demonstrated that nicotine extends life-span in paraquat-treated Drosophila (P=4E-30). Brain tissue from flies treated with combinations of paraquat and nicotine revealed elevated expression of CG14691 with paraquat which was restored with nicotine co-treatment (P(interaction)=2E-11, P(FDR-adjusted)=4E-7). Independently, variants in the 5’ region of SV2C, a human ortholog of CG14691, gave the strongest signal for interaction with smoking (P(interaction)=9E-8). The effect of smoking on PD risk varied six-fold by SV2C genotype (P(heterogeneity)=4E-10). Moreover, SV2C variants identified here were associated with SVC2 gene-expression in the HapMap data. Present results suggest synaptic vesicle protein SV2C plays a role in PD pathogenesis, and that the SV2C genotype may be useful for clinical trials of nicotine for treating PD.
2012-09-05 | GSE35930 | GEO
Project description:Neural tube defects (NTD) occur in 3000 births per year in the US. Several risk factors have been proposed for NTDs including both first hand and passive smoking during the periconceptual period. Previously we reported an increased frequency of cervical region NTD in a chicken model of prenatal nicotine exposure (Bohn, Humphrey et al. 2014; Humprey, Bohn et al. 2014). Here, we will reveal the mechanisms of the insult. The specific aims include: 1) Evaluation of the gene expression changes in the chicken model of nicotine exposure that we developed previosly. Such genome-wide analysis of the expression allows to collect very detailed data regarding the drug impact. To our knowlidge, comparable analysis of nicotine induced changes in gene expression during development of any species has never been conducted. 2) Evaluation of nicotine induced alterations in tadpoles (Xenopus tropica). The frogs will be treated in a manner similar to chicken (the same drug doses and a matched time of sacrifice) and analyzed both histologically and for gene expression. Incorporation of a different group of vertebrates in this study is essential for dissecting the evolutionary conserved role this pathway of interest in development which is another strong aspect of this proposal. We believe, that our comparative approach will allow more effective extrapolation of data from animal models to humans and better understanding of the evolutionary process. Nicotine is one of the most common developmental insults in humans. The consequences of this exposure are well-documented. However, the affected pathways are unknown. The identification of the mechanisms of nicotine induced alterations proposed here is vital for development of better treatment strategies.
2020-09-11 | GSE103703 | GEO