It has become clear that early life (including in utero exposures) is a key window of vulnerability during which environmental exposures can alter developmental trajectories and initiate allergic disease development. However, recent evidence suggests that there might be additional windows of vulnerability to environmental exposures in the parental generation before conception or even in previous generations. There is evidence suggesting that information of prior exposures can be transferred across generations, and experimental animal models suggest that such transmission can be conveyed through epigenetic mechanisms. Although the molecular mechanisms of intergenerational and transgenerationational epigenetic transmission have yet to be determined, the realization that environment before conception can alter the risks of allergic diseases has profound implications for the development of public health interventions to prevent disease. Future research in both experimental models and in multigenerational human cohorts is needed to better understand the role of intergenerational and transgenerational effects in patients with asthma and allergic disease. This will provide the knowledge basis for a new approach to efficient intervention strategies aimed at reducing the major public health challenge of these conditions.
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.
This study was conducted in Kinondoni district, Dar es Salaam, Tanzania, with the objectives to generate prediction equations for forced expiratory volume in 1 second (FEV1), forced expiratory volume in 6 seconds (FEV6), FEV1/FEV6 ratio and peak expiratory flow (PEF) from a nonsymptomatic sample of the population, and to compare these equations to published reference values. The study included adults aged ≥ 15 years who were recruited by use of community based, multistage cluster random sampling. Participants performed spirometry and answered questionnaires regarding respiratory symptoms and socioeconomic conditions. Anthropometric data were collected. Selection of subjects for generation of reference values followed American Thoracic Society (ATS) recommendations. Data were analyzed using multiple regression techniques. Fifty two men and 98 women were selected to the reference value group. FEV1, FEV6, FEV1/FEV6 and PEF were regressed against age, height and weight. For men a curvilinear model was chosen when predicting FEV1, FEV6 and PEF, and a linear model predicted FEV1/FEV6. For women a linear model was used in the regression equations. The reference values generated from our study were lower than in several previously published studies. Our study suggests that assessment of respiratory function should be based on reference values generated from the same population as those being assessed. ______________________________________________________________________________________
Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood.
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