Early moderate prenatal alcohol exposure and maternal diet impact offspring DNA methylation across species.

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in newborn pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.

Drinking excessive amounts of alcohol during pregnancy can cause foetal alcohol spectrum disorder and other conditions in children that affect their physical and mental development. Many countries advise women who are pregnant or trying to conceive to avoid drinking alcohol entirely. However, surveys of large groups of women in Western countries indicate that most women continue drinking low to moderate amounts of alcohol until they discover they are pregnant and then stop consuming alcohol for the rest of their pregnancy. It remains unclear how this common drinking pattern affects the foetus. The instructions needed to build and maintain a human body are stored within molecules of DNA. Some regions of DNA called genes contain the instructions to make proteins, which perform many tasks in the body. Other so-called 'non-coding' regions do not code for any proteins but instead have roles in regulating gene activity. One way cells control which genes are switched on or off is adding or removing tags known as methyl groups to certain locations on DNA. Previous studies indicate that alcohol may affect how children develop by changing the patterns of methyl tags on DNA. To investigate the effect of moderate drinking during the early stages of pregnancy, Bestry et al. exposed pregnant mice to alcohol and examined how this affected the patterns of methyl tags on DNA in their offspring. The experiments found moderate levels of alcohol were sufficient to alter the patterns of methyl tags in the brains and livers of the newborn mice. Most of the changes were observed in non-coding regions of DNA, suggesting alcohol may affect how large groups of genes are regulated. Fewer changes in the patterns of methyl tags were found in mice whose mothers had diets rich in two essential nutrients known as folate and choline. Further experiments found that some of the affected mouse genes were similar to genes linked to foetal alcohol spectrum disorder and other related conditions in humans. These findings highlight the potential risks of consuming even moderate levels of alcohol during pregnancy and suggest that a maternal diet rich in folate and choline may help mitigate some of the harmful effects on the developing foetus.

Electronic Cigarette Usage Patterns and Perceptions in Adult Australians.

Despite their increasing popularity, and Australia's unique regulatory environment, how and why Australian adults use e-cigarettes and their perceptions of their safety, efficacy and regulation have not been extensively reported before. In this study, we screened 2217 adult Australians with the aim of assessing these questions in a sample of current or former e-cigarette users. A total of 505 out of 2217 respondents were current or former e-cigarette users, with only these respondents completing the full survey. Key findings of this survey included the high proportion of respondents who indicated they were currently using e-cigarettes (307 out of 2217 = 13.8%), and the high proportion of current e-cigarette users that were also smokers (74.6%). The majority of respondents used e-liquids containing nicotine (70.3%), despite it being illegal in Australia without a prescription, and the majority bought their devices and liquids in Australia (65.7%). Respondents reported using e-cigarettes in a variety of places, including inside the home, inside public places (where it is illegal to smoke tobacco cigarettes), and around other people-which has implications for second and third hand exposures. A significant proportion of current e-cigarette users (30.6%) thought that e-cigarettes were completely safe to use long-term, although in general, there was a large amount of uncertainty/ambivalence with respect to perceptions of e-cigarette safety and efficacy as smoking cessation tools. This study shows that e-cigarette use is common in Australia, and that appropriate dissemination of unbiased research findings on their safety and efficacy in smoking cessation is urgently required.

Long-term exposure of mice to 890 ppm atmospheric CO2 alters growth trajectories and elicits hyperactive behaviours in young adulthood.

Atmospheric carbon dioxide (CO2 ) levels are currently at 418 parts per million (ppm), and by 2100 may exceed 900 ppm. The biological effects of lifetime exposure to CO2 at these levels is unknown. Previously we have shown that mouse lung function is altered by long-term exposure to 890 ppm CO2 . Here, we assess the broader systemic physiological responses to this exposure. Mice were exposed to either 460 or 890 ppm from preconception to 3 months of age, and assessed for effects on developmental, renal and osteological parameters. Locomotor, memory, learning and anxiety-like behaviours of the mice were also assessed. Exposure to 890 ppm CO2 increased birthweight, decreased female body weight after weaning, and, as young adults, resulted in reduced engagement in memory/learning tasks, and hyperactivity in both sexes in comparison to controls. There were no clear anxiety, learning or memory changes. Renal and osteological parameters were minimally affected. Overall, this study shows that exposure of mice to 890 ppm CO2 from preconception to young adulthood alters growth and some behaviours, with limited evidence of compensatory changes in acid-base balance. These findings highlight the potential for a direct effect of increased atmospheric CO2 on mammalian health outcomes. KEY POINTS: Long-term exposure to elevated levels of atmospheric CO2 is an uncontrolled experiment already underway. This is the first known study to assess non-respiratory physiological impacts of long-term (conception to young adulthood) exposure of mice to CO2 at levels that may arise in the atmosphere due to global emissions. Exposure to elevated CO2 , in comparison to control mice, altered growth patterns in early life and resulted in hyperactive behaviours in young adulthood. Renal and bone parameters, which are important to balance acid-base levels to compensate for increased CO2 exposure, remained relatively unaffected. This work adds to the body of evidence regarding the effects of carbon emissions on mammalian health and highlights a potential future burden of disease.

Mouse Lung Structure and Function after Long-Term Exposure to an Atmospheric Carbon Dioxide Level Predicted by Climate Change Modeling.

BACKGROUND: Climate change models predict that atmospheric carbon dioxide [CO2] levels will be between 700 and 900 ppm within the next 80 y. Despite this, the direct physiological effects of exposure to slightly elevated atmospheric CO2 (as compared with ∼410 ppm experienced today), especially when exposures extend from preconception to adulthood, have not been thoroughly studied. OBJECTIVES: In this study we aimed to assess the respiratory structure and function effects of long-term exposure to 890 ppm CO2 from preconception to adulthood using a mouse model. METHODS: We exposed mice to CO2 (∼890 ppm) from prepregnancy, through the in utero and early life periods, until 3 months of age, at which point we assessed respiratory function using the forced oscillation technique, and lung structure. RESULTS: CO2 exposure resulted in a range of respiratory impairments, particularly in female mice, including higher tissue elastance, longer chord length, and lower lung compliance. Importantly, we also assessed the lung function of the dams that gave birth to our experimental subjects. Even though these mice had been exposed to the same level of increased CO2 for a similar amount of time (∼8wk), we measured no impairments in lung function. This suggests that the early life period, when lungs are undergoing rapid growth and development, is particularly sensitive to CO2. DISCUSSION: To the best of our knowledge, this study, for the first time, shows that long-term exposure to environmentally relevant levels of CO2 can impact respiratory function in the mouse. https://doi.org/10.1289/EHP7305.

The Evolving Landscape of e-Cigarettes: A Systematic Review of Recent Evidence.

Smoking continues to be a burden to economies and health-care systems across the world. One proposed solution to the problem has been e-cigarettes; however, because they are a relatively new product in the market, little is known about their potential health impacts. Furthermore, e-cigarettes continue to evolve at a rapid rate, making it necessary to regularly review and summarize available studies. Although e-cigarettes are marketed as a smoking cessation tool by some manufacturers, the reality is that many nonsmokers, including youth, are using them. This review focuses on two major demographic groups (smokers and nonsmokers) and evaluates the most recent data (early 2017 to mid 2019) regarding the potential health effects of e-cigarettes. We assessed peer-reviewed studies on the health impacts of e-cigarettes, with a particular focus on common questions asked by policy makers, clinicians, and scientists: (1) What are the effects of e-cigarettes compared with air/not smoking?; (2) Is there any direct evidence of harm or benefit to humans?; (3) Is there a risk from secondhand exposure?; (4) What are the risks and/or benefits of e-cigarettes compared with tobacco cigarette use?; (5) Are there risks or benefits to specific populations (eg, people with COPD or asthma, pregnant women [and their offspring])?; (6) What are the effects of flavoring chemicals?; (7) What are the effects of including nicotine in e-liquids?; (8) How often is nicotine concentration labeling incorrect?; and (9) What are the risks when e-cigarettes explode?

Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice).

BACKGROUND: Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life. METHODS: Female C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age. RESULTS: A high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam's diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid. CONCLUSIONS: While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings.