Ardie Barry Sailis

E‐cigarette devices emit ultrafine metal‐containing particles from heating coils, solder joints, and other wetted components, but their reproductive toxicology remains poorly defined. This review integrates evidence from aerosol chemistry, nanoparticle toxicology, and male reproductive biology to evaluate whether these particles may contribute to male reproductive dysfunction through mitochondrial injury. E‐cigarette aerosols can contain nanoscale and ultrafine particles bearing chromium, nickel, iron, copper, zinc, tin, and lead. These particles may deposit in the distal lung and, based on broader nanoparticle toxicokinetics, could enter the systemic circulation. However, direct particle‐resolved evidence of their accumulation in testicular tissue is currently absent. Mechanistic evidence therefore derives mainly from engineered nanoparticle and soluble‐metal models. These studies indicate that metal exposure can disrupt blood–testis barrier integrity, impair Sertoli‐ and Leydig‐cell function, alter steroidogenesis, damage germ cells, and reduce sperm quality. Mitochondria represent a plausible point of convergence because particle‐ and ion‐mediated mechanisms can promote mitochondrial reactive oxygen species generation, lipid peroxidation, respiratory dysfunction, mitochondrial DNA damage, altered fusion–fission balance, defective mitophagy, apoptosis, and inflammatory signaling. These pathways provide a biologically plausible framework linking inhaled metal‐containing particles to impaired spermatogenesis and steroidogenesis, without establishing causality under realistic vaping conditions. Future studies should combine inhalation‐relevant exposure models with particle‐resolved biodistribution, dosimetry, and mechanistic reproductive endpoints to determine whether these pathways operate following e‐cigarette exposure.

E-cigarette use has increased substantially, particularly among adolescents and young adults, yet its long-term respiratory effects remain incompletely understood. E-cigarette aerosol contains biologically active constituents, including nicotine, propylene glycol, vegetable glycerin, flavoring chemicals, aldehydes, metals, particles, and reactive oxygen species, which may disrupt respiratory epithelial homeostasis. This review synthesizes experimental, preclinical, and human-relevant evidence linking e-cigarette aerosol exposure to respiratory epithelial injury, with emphasis on ferroptosis-related mechanisms. Available evidence indicates that e-cigarette aerosol can impair epithelial barrier integrity, alter mucociliary defense, increase MUC5AC expression, induce oxidative stress, and promote inflammatory signaling. Emerging preclinical data suggest that electronic nicotine delivery system exposure may induce ferroptosis-associated lung injury through increased CD71/TFR1 and ACSL4 expression, reduced GPX4, altered lipid profiles, BODIPY-C11-positive lipid peroxidation, epithelial cell death, inflammation, mucus accumulation, emphysema-like pathology, and fibrosis. Mechanistically, e-cigarette aerosol may create a ferroptosis-permissive epithelial environment by promoting redox imbalance, GPX4/GSH/SLC7A11 antioxidant defense impairment, altered iron handling, ACSL4-mediated PUFA-phospholipid remodeling, NRF2/ARE stress responses, mitochondrial dysfunction, and lipid peroxide accumulation. Ferroptotic epithelial injury may further amplify airway inflammation and remodeling through DAMP release, macrophage recruitment, cytokine production, barrier disruption, mucus dysregulation, and extracellular matrix deposition. However, direct human evidence remains limited, and many mechanistic links are extrapolated from cigarette smoke, particulate matter, and broader lung injury models. Future studies should use standardized exposure systems, human-relevant airway and alveolar models, comprehensive ferroptosis markers, and ferroptosis-specific rescue experiments to determine whether ferroptosis is a driver, amplifier, or downstream marker of e-cigarette-associated respiratory injury.

Electronic cigarettes are widely used by individuals in their reproductive years, yet polymer materials in pods, wicks, seals, and casings remain underexamined as possible contributors to inhaled particulate exposure. This narrative review evaluates whether e-cigarette device components could plausibly generate microplastics or nanoplastics during use and whether such particles, if present, could have reproductive relevance. Evidence from device-material studies, polymer degradation chemistry, aerosol physics, inhalation toxicology, and reproductive microplastic models was synthesized. Current devices place polycarbonate, polydimethylsiloxane, nylon, and other polymers near heating and aerosolization zones, where thermal cycling, solvent contact, and mechanical stress could theoretically promote oxidation, chain scission, embrittlement, or fragmentation. However, no study has chemically identified or quantified device-derived microplastics or nanoplastics in e-cigarette aerosols using polymer-resolving methods. Thus, links between e-cigarette use, inhaled polymer particles, and reproductive harm remain hypothetical. Evidence from non-e-cigarette models shows that micro- and nanoplastics can induce oxidative stress, inflammation, endocrine disruption, barrier interaction, and cellular injury, but these findings cannot be extrapolated without confirming particle formation, polymer identity, dose, and biodistribution. Future research should prioritize polymer-resolved aerosol testing under realistic puffing regimens, including unused and aged devices, e-liquids, condensates, and emitted aerosols. Key endpoints should include polymer identity, particles per puff, particles per mL of e-liquid consumed, particle size distribution, polymer mass, pulmonary deposition, systemic translocation, and reproductive or placental effects. Device-derived microplastics should be treated as a plausible particle-safety concern requiring direct experimental evaluation.

Electronic cigarettes are widely promoted as harm-reduction alternatives to conventional tobacco smoking, yet their potential effects on male sexual health remain incompletely characterised. Erectile dysfunction is a predominantly vascular condition with important neuroendocrine regulation and is highly sensitive to endothelial injury, oxidative stress, hormonal imbalance, and autonomic dysregulation, all of which may plausibly be influenced by electronic cigarette use. Despite increasing global prevalence, direct evidence linking electronic cigarette use to erectile dysfunction remains limited. This narrative review synthesises current experimental, clinical, and epidemiological evidence examining the association between electronic cigarette use and erectile dysfunction, with emphasis on underlying biological mechanisms and key research gaps. Emerging evidence implicates endothelial dysfunction, impaired nitric oxide bioavailability, oxidative stress, inflammation, hormonal disturbance, autonomic imbalance, sleep disturbance, and exposure to aerosolised substances and metals as interconnected pathways that may contribute to erectile dysfunction. Overall, the existing literature remains preliminary and largely hypothesis-generating, with no longitudinal studies capable of establishing causality or dose-response relationships. Well-designed prospective studies are required to clarify the long-term sexual health outcomes associated with electronic cigarette use.

1. IntroductionElectronic cigarettes have rapidly reshaped global nicotine use, particularly among adolescents and young adults, due to their perceived safety, technical customizability, and extens...

Background: Obesity and erectile dysfunction (ED) are increasingly co‐prevalent, yet adipose tissue is often viewed as a secondary contributor rather than a primary driver of erectile impairment. Objective: To evaluate an adipose‐centric framework in which depot‐specific adipose dysfunction regulates vascular, neuroendocrine, and smooth muscle processes essential for erection. Methods: A narrative synthesis of mechanistic, preclinical, and clinical studies was conducted, focusing on inflammation, cellular senescence, extracellular vesicle signaling, ferroptosis, mitochondrial dysfunction, and glycocalyx injury across visceral, perivascular, and periprostatic adipose depots. Results: Dysfunctional adipose tissue remodels systemic and local microenvironments through adipokines, cytokines, extracellular vesicle cargo, and oxidized lipid mediators. These processes reduce nitric oxide bioavailability, increase vascular stiffness, disrupt neuroendocrine signaling, and promote cavernosal fibrosis. Perivascular adipose tissue exerts localized effects on penile hemodynamics. Clinical and genetic evidence supports a causal link between central adiposity and ED, while weight loss and adipose‐targeted interventions improve erectile outcomes. Conclusion: Adipose tissue functions as an upstream regulator of ED pathogenesis. Targeting adipose dysfunction through lifestyle, pharmacological, and emerging strategies such as senolytics and extracellular vesicle modulation may modify disease progression rather than provide symptomatic relief.

Transcriptional regulation is commonly viewed through the spatial organization of enhancers, promoters, and chromatin architecture, yet this perspective does not fully explain how cells decode dynamic signaling inputs over time. This review proposes that biomolecular condensates provide a mechanistic framework for temporal signal decoding in gene regulation. Current evidence indicates that transcriptional condensates formed by phase separation concentrate transcription factors, cofactors, and RNA polymerase II at regulatory loci, while their threshold-dependent assembly, nucleation delay, molecular exchange, and persistence may enable temporal integration of signaling inputs, filtering of rapid fluctuations, and modulation of transcriptional bursting. In addition, signaling-dependent post-translational modifications, metabolic state, and physicochemical conditions are discussed as key regulators of condensate material properties and responsiveness. Experimental strategies, including live-cell imaging, optogenetic perturbation, and quantitative kinetic analysis, are outlined to test this framework and establish causal links between signaling dynamics, condensate behavior, and transcriptional output. Together, these observations support a spatiotemporal model of transcription in which biomolecular condensates act as candidate intermediaries linking dynamic signaling inputs to coherent gene expression programs, with implications for development, cell fate decisions, and disease.