Multigenerational nicotine exposure affects offspring nicotine metabolism, nicotine-induced hypothermia, and basal corticosterone in a sex-dependent manner

Zeid, Dana; Goldberg, Lisa R.; Seemiller, Laurel R.; Mooney‐Leber, Sean M.; Smith, Philip B.; Gould, Thomas J.

doi:10.1016/j.ntt.2021.106972

Cited by 10 publications

(12 citation statements)

References 21 publications

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“…A consistent theme across these findings was the regulation of psychological stress at the level of behavior and underlying physiology. Of note, we previously found that paternal nicotine exposure predicted reduced basal serum corticosterone in F1 offspring [8].…”

Section: Literature Review Of Differentially Expressed Sperm Mirnasmentioning

confidence: 78%

“…Thus, mRNA targets of these differentially expressed sperm miRNAs may illuminate biological pathways mediating phenotypic dysregulation in the F1 generation. Using the same nicotine exposure model employed here, we previously found that offspring of exposed males exhibited altered hippocampal functioning, hippocampus-dependent learning, nicotine-seeking, nicotine metabolism, and basal stress hormones [7,8]. In addition to presenting our comprehensive sperm small RNA sequencing data, we further aimed to interpret these data within the context of our previously published extensive F1 phenotyping.…”

Section: Discussionmentioning

confidence: 98%

“…Evidence from animal models of nicotine-induced multigenerational inheritance suggests broad phenotypic dysregulation in offspring of nicotine-exposed males [3][4][5][6]. We previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones [7,8]. However, biological mechanisms involved in these multigenerational effects have yet to be fully elucidated [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

Zeid¹,

Gould²

2022

Preprint

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Multigenerational inheritance is a non-genomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using biological enrichment analysis, which also supported enrichment of gene expression pathways involved in hippocampus-dependent learning. Our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model. Specifically, differentially expressed F0 sperm miRNAs may regulate the previously observed changes in F1 learning and stress. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.

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Section: Literature Review Of Differentially Expressed Sperm Mirnasmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

Zeid¹,

Gould²

2022

Preprint

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“…Various studies have demonstrated that nicotine negatively affects endocrine processes such as those related to the HPG, HPA, and HPT axes and thus causes dysfunction of their hormonal homeostasis [21,26,31,32,34,35,49]. The HPG, HPA, and HPT axes involve hypothalamic and pituitary coordination for the regulation of the synthesis and secretion of gonadal steroid, adrenal corticosteroid, and thyroid hormones, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Despite a decline of about 30% in smoking prevalence in the adult population over the last 30 years, tobacco smoking (both active and passive) continues to play havoc with as Grave's disease and goiters are also predisposed by smoking [17,21]. Smoking induces stress and increases cortisol levels in the blood and thus interferes with stress response, immunological function, and inflammatory responses [33][34][35]. Smoking during pregnancy is associated with developmental and functional problems of the fetus and in addition, predisposes the newborns to adult-onset health consequences [36].…”

Section: Introductionmentioning

confidence: 99%

Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches

Rehan

Zargar

Sheikh

et al. 2022

Toxics

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Tobacco/nicotine is one of the most toxic and addictive substances and continues to pose a significant threat to global public health. The harmful effects of smoking/nicotine affect every system in the human body. Nicotine has been associated with effects on endocrine homeostasis in humans such as the imbalance of gonadal steroid hormones, adrenal corticosteroid hormones, and thyroid hormones. The present study was conducted to characterize the structural binding interactions of nicotine and its three important metabolites, cotinine, trans-3′-hydroxycotinine, and 5′-hydroxycotinine, against circulatory hormone carrier proteins, i.e., sex-hormone-binding globulin (SHBG), corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG). Nicotine and its metabolites formed nonbonded contacts and/or hydrogen bonds with amino acid residues of the carrier proteins. For SHBG, Phe-67 and Met-139 were the most important amino acid residues for nicotine ligand binding showing the maximum number of interactions and maximum loss in ASA. For CBG, Trp-371 and Asn-264 were the most important amino acid residues, and for TBG, Ser-23, Leu-269, Lys-270, Asn-273, and Arg-381 were the most important amino acid residues. Most of the amino acid residues of carrier proteins interacting with nicotine ligands showed a commonality with the interacting residues for the native ligands of the proteins. Taken together, the results suggested that nicotine and its three metabolites competed with native ligands for binding to their carrier proteins. Thus, nicotine and its three metabolites may potentially interfere with the binding of testosterone, estradiol, cortisol, progesterone, thyroxine, and triiodothyronine to their carrier proteins and result in the disbalance of their transport and homeostasis in the blood circulation.

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Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

Zeid

Gould

2023

Developmental Psychobiology

Self Cite

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Multigenerational inheritance is a nongenomic form of heritability characterized by altered phenotypes in the first generation born from the exposed parent. Multigenerational factors may account for inconsistencies and gaps in heritable nicotine addiction vulnerability. Our lab previously found that F1 offspring of male C57BL/6J mice chronically exposed to nicotine exhibited altered hippocampus functioning and related learning, nicotine-seeking, nicotine metabolism, and basal stress hormones. In an effort to identify germline mechanisms underlying these multigenerational phenotypes, the current study sequenced small RNA extracted from sperm of males chronically administered nicotine using our previously established exposure model. We identified 16 miRNAs whose expression in sperm was dysregulated by nicotine exposure. A literature review of previous research on these transcripts suggested an enrichment for regulation of psychological stress and learning. mRNAs predicted to be regulated by differentially expressed sperm small RNAs were further analyzed using exploratory enrichment analysis, which suggested potential modulation of pathways related to learning, estrogen signaling, and hepatic disease, among other findings. Overall, our findings point to links between nicotine-exposed F0 sperm miRNA and altered F1 phenotypes in this multigenerational inheritance model, particularly F1 memory, stress, and nicotine metabolism. These findings provide a valuable foundation for future functional validation of these hypotheses and characterization of mechanisms underlying male-line multigenerational inheritance.

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Multigenerational nicotine exposure affects offspring nicotine metabolism, nicotine-induced hypothermia, and basal corticosterone in a sex-dependent manner

Cited by 10 publications

References 21 publications

Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

Chronic nicotine exposure alters sperm small RNA content in a C57BL/6J mouse model: Implications for multigenerational inheritance

Potential Disruption of Systemic Hormone Transport by Tobacco Alkaloids Using Computational Approaches

Chronic nicotine exposure alters sperm small RNA content in C57BL/6J mouse model

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