Preconceptional smoking alters spermatozoal miRNAs of murine fathers and affects offspring’s body weight

Background Active smoking has been reported among 7% of teenagers worldwide, with ages ranging from 13 to 15 years. An epidemiological study suggested that preconceptional paternal smoking is associated with adolescent obesity in boys. We developed a murine adolescent smoking model before conception to investigate the paternal molecular causes of changes in offspring’s phenotype. Method Male and female C57BL/6J mice were exposed to increasing doses of mainstream cigarette smoke (CS) from onset of puberty for 6 weeks and mated with room air (RA) controls. Results Thirteen miRNAs were upregulated and 32 downregulated in the spermatozoa of CS-exposed fathers, while there were no significant differences in the count and morphological integrity of spermatozoa, as well as the proliferation of spermatogonia between CS- and RA-exposed fathers. Offspring from preconceptional CS-exposed mothers had lower body weights (p = 0.007). Moreover, data from offspring from CS-exposed fathers suggested a potential increase in body weight (p = 0.062). Conclusion We showed that preconceptional paternal CS exposure regulates spermatozoal miRNAs, and possibly influences the body weight of F1 progeny in early life. The regulated miRNAs may modulate transmittable epigenetic changes to offspring, thus influence the development of respiratory- and metabolic-related diseases such as obesity, a mechanism that warrants further studies for elaborate explanations

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Long-Term Effects of the Periconception Period on Embryo Epigenetic Profile and Phenotype: The Role of Stress and How This Effect Is Mediated

Stress represents an unavoidable aspect of human life, and pathologies associated with dysregulation of stress mechanisms - particularly psychiatric disorders - represent a significant global health problem. While it has long been observed that levels of stress experienced in the periconception period may greatly affect the offspring's risk of psychiatric disorders, the mechanisms underlying these associations are not yet comprehensively understood. In order to address this question, this chapter will take a 'top-down' approach, by first defining stress and associated concepts, before exploring the mechanistic basis of the stress response in the form of the hypothalamic-pituitary-adrenal (HPA) axis, and how dysregulation of the HPA axis can impede our mental and physical health, primarily via imbalances in glucocorticoids (GCs) and their corresponding receptors (GRs) in the brain. The current extent of knowledge pertaining to the impact of stress on developmental programming and epigenetic inheritance is then extensively discussed, including the role of chromatin remodelling associated with specific HPA axis-related genes and the possible role of regulatory RNAs as messengers of environmental stress both in the intrauterine environment and across the germ line. Furthering our understanding of the role of stress on embryonic development is crucial if we are to increase our predictive power of disease risk and devise-effective treatments and intervention strategies

Smoking‐induced genetic and epigenetic alterations in infertile men

Male fertility rates have shown a progressive decrease in both developing and industrialised countries in the past 50 years. Clinical and epidemiological studies have demonstrated controversial results about the harmful effects of cigarette smoking on seminal parameters. Some studies could not establish a negative effect by tobacco smoking on sperm quality and function, whereas others have found a significant reduction in sperm quality and function. This study reviews the components in cigarette smoke and discusses the effects of smoking on male fertility by focusing extensively on smoking‐induced genetic and epigenetic alterations in infertile men. Chromosomal aneuploidies, sperm DNA fragmentation and gene mutations are discussed in the first section, while changes in DNA methylation, chromatin remodelling and noncoding RNAs are discussed in the second section as part of epigenetic alterations

Ambient air pollution and thrombosis

Abstract Air pollution is a growing public health concern of global significance. Acute and chronic exposure is known to impair cardiovascular function, exacerbate disease and increase cardiovascular mortality. Several plausible biological mechanisms have been proposed for these associations, however, at present, the pathways are incomplete. A seminal review by the American Heart Association (2010) concluded that the thrombotic effects of particulate air pollution likely contributed to their effects on cardiovascular mortality and morbidity. The aim of the current review is to appraise the newly accumulated scientific evidence (2009–2016) on contribution of haemostasis and thrombosis towards cardiovascular disease induced by exposure to both particulate and gaseous pollutants. Seventy four publications were reviewed in-depth. The weight of evidence suggests that acute exposure to fine particulate matter (PM2.5) induces a shift in the haemostatic balance towards a pro-thrombotic/pro-coagulative state. Insufficient data was available to ascertain if a similar relationship exists for gaseous pollutants, and very few studies have addressed long-term exposure to ambient air pollution. Platelet activation, oxidative stress, interplay between interleukin-6 and tissue factor, all appear to be potentially important mechanisms in pollution-mediated thrombosis, together with an emerging role for circulating microvesicles and epigenetic changes. Overall, the recent literature supports, and arguably strengthens, the contention that air pollution contributes to cardiovascular morbidity by promoting haemostasis. The volume and diversity of the evidence highlights the complexity of the pathophysiologic mechanisms by which air pollution promotes thrombosis; multiple pathways are plausible and it is most likely they act in concert. Future research should address the role gaseous pollutants play in the cardiovascular effects of air pollution mixture and direct comparison of potentially susceptible groups to healthy individuals

A systematic review of outdoor airborne fungal spore seasonality across Europe and the implications for health

Fungal spores make up a significant proportion of organic matter within the air. Allergic sensitisation to fungi is associated with conditions including allergic fungal airway disease. This systematic review analyses outdoor fungal spore seasonality across Europe and considers the implications for health. Seventy-four studies met the inclusion criteria, the majority of which (n = 64) were observational sampling studies published between 1978 and 2020. The most commonly reported genera were the known allergens Alternaria and Cladosporium, measured in 52 and 49 studies, respectively. Both displayed statistically significant increased season length in south-westerly (Mediterranean) versus north-easterly (Atlantic and Continental) regions. Although there was a trend for reduced peak or annual Alternaria and Cladosporium spore concentrations in more northernly locations, this was not statistically significant. Peak spore concentrations of Alternaria and Cladosporium exceeded clinical thresholds in nearly all locations, with median peak concentrations of 665 and 18,827 per m3, respectively. Meteorological variables, predominantly temperature, precipitation and relative humidity, were the main factors associated with fungal seasonality. Land-use was identified as another important factor, particularly proximity to agricultural and coastal areas. While correlations of increased season length or decreased annual spore concentrations with increasing average temperatures were reported in multi-decade sampling studies, the number of such studies was too small to make any definitive conclusions. Further, up-to-date studies covering underrepresented geographical regions and fungal taxa (including the use of modern molecular techniques), and the impact of land-use and climate change will help address remaining knowledge gaps. Such knowledge will help to better understand fungal allergy, develop improved fungal spore calendars and forecasts with greater geographical coverage, and promote increased awareness and management strategies for those with allergic fungal disease.</p