Impact Of Environmental Toxicants Research Articles

Utilizing latent connectivity among mediators in high‐dimensional mediation analysis

Mediation analysis intends to unveil the underlying relationship between an outcome variable and an exposure variable through one or more intermediate variables called mediators. In recent decades, research on mediation analysis has been focusing on multivariate mediation models, where the number of mediating variables is possibly of high dimension. This paper concerns high‐dimensional mediation analysis and proposes a three‐step algorithm that extracts and utilizes inter‐connectivity among candidate mediators. More specifically, the proposed methodology starts with a screening procedure to reduce the dimensionality of the initial set of candidate mediators, followed by a penalized regression model that incorporates both parameter‐ and group‐wise regularization, and ends with fitting a multivariate mediation model and identifying active mediating variables through a joint significance test. To showcase the performance of the proposed algorithm, we conducted two simulation studies in high‐dimensional and ultra‐high‐dimensional settings, respectively. Furthermore, we demonstrate the practical applications of the proposal using a real data set that uncovers the possible impact of environmental toxicants on women's gestational age at delivery through 61 biomarkers that belong to 7 biological pathways.

Environmental impact on reproductive health and risk mitigating strategies.

The purpose of this review is to increase awareness among reproductive health professionals and trainees about the impact of environmental toxicants and climate change on women's health and mitigation strategies at the individual, professional and governmental levels. Global health indicators reveal a meteoric rise of noncommunicable diseases over the past 50 years, which threaten reproductive health directly and indirectly. Evolutionary genetic mutations as contributors are unlikely in this timeframe, and environmental causes have been invoked. Notably, the past 75 years have witnessed marked increases in industrial chemical production, and global warming has rendered a 'climate crisis' with extreme temperatures and compromised food, water, and air quality. There is now strong experimental and epidemiologic evidence for endocrine disrupting chemicals and particulate matter and chemical components of air pollution in the pathophysiology of human reproductive disorders during development and across the lifespan, especially among vulnerable populations. Environmental impacts on fertility, pregnancy outcomes, childhood neurodevelopment, and reproductive tract development are significant, not widely appreciated, and may be preventable. In light of the evidence, education and advocating economical mitigations of toxic environmental chemicals and alternative energy strategies are imperatives to assure quality reproductive health for this and future generations.

A needs assessment on addressing environmental health issues within reproductive health service provision: Considerations for continuing education and support

This needs assessment was initially undertaken to explore the beliefs and knowledge of nurses and physicians about the impact of environmental toxicants on maternal and infant health, as well as to describe current practice and needs related to addressing environmental health issues (EHI). One hundred and thirty-five nurses (n = 99) and physicians (n = 36) working in Saskatchewan completed an online survey. Survey questions were designed to determine how physicians and nurses think about and incorporate environmental health issues into their practice and means of increasing their capacity to do so. Although participants considered it important to address EHIs with patients, in actual practice they do so with only moderate frequency. Participants reported low levels of knowledge about EHIs' impact on health, and low levels of confidence discussing them with patients. Participants requested additional information on EHIs, especially in the form of online resources. The results suggests that while nurses and physicians consider EHIs important to address with patients, more education, support, and resources would increase their capacity to do so effectively. Based on the findings, considerations and recommendations for continuing education in this area have been provided.

TCDD influences reservoir of antibiotic resistance genes in murine gut microbiome.

Dysbiosis of the gut microbiome via antibiotics, changes in diet and infection can select for bacterial groups that more frequently harbor antimicrobial resistance genes (ARGs) and mobile genetic elements (MGEs). However, the impact of environmental toxicants on the reservoir of ARGs in the gut microbiome has received less attention. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent aryl hydrocarbon receptor (AhR) agonist with multiple toxic health effects including immune dysfunction. The selective pressure of TCDD on the abundance of ARG and MGE-harboring gut populations was examined using C57BL/6 mice exposed to 0-30 μg/kg TCDD for 28 and 92 days with the latter having a 30-day recovery period. DNA extracted from temporally collected fecal pellets was characterized using a qPCR array with 384 assays targeting ARGs and MGEs. Fourteen genes, typically observed in Enterobacteriaceae, increased significantly within 8 days of initial dosing, persisted throughout the treatment period, and remained induced 30 days post dosing. A qPCR primer set targeting Enterobacteriaceae also showed 10- to 100-fold higher abundance in TCDD-treated groups, which was further verified using metagenomics. Results show a bloom of ARG-harboring bacterial groups in the gut due to a xenobiotic compound that is not a metal, biocide or antimicrobial.

Influence of environmental exposure on human epigenetic regulation.

Environmental toxicants can alter epigenetic regulatory features such as DNA methylation and microRNA expression. As the sensitivity of epigenomic regulatory features may be greatest during the in utero period, when critical windows are narrow, and when epigenomic profiles are being set, this review will highlight research focused on that period. I will focus on work in human populations, where the impact of environmental toxicants in utero, including cigarette smoke and toxic trace metals such as arsenic, mercury and manganese, on genome-wide, gene-specific DNA methylation has been assessed. In particular, arsenic is highlighted, as this metalloid has been the focus of a number of studies and its detoxification mechanisms are well understood. Importantly, the tissues and cells being examined must be considered in context in order to interpret the findings of these studies. For example, by studying the placenta, it is possible to identify potential epigenetic adaptations of key genes and pathways that may alter the developmental course in line with the developmental origins of health and disease paradigm. Alternatively, studies of newborn cord blood can be used to examine how environmental exposure in utero can impact the composition of cells within the peripheral blood, leading to immunological effects of exposure. The results suggest that in humans, like other vertebrates, there is a susceptibility for epigenomic alteration by the environment during intrauterine development, and this may represent a mechanism of plasticity of the organism in response to its environment as well as a mechanism through which long-term health consequences can be shaped.

The effects of environmental toxins on allergic inflammation.

The prevalence of asthma and allergic disease has increased worldwide over the last few decades. Many common environmental factors are associated with this increase. Several theories have been proposed to account for this trend, especially those concerning the impact of environmental toxicants. The development of the immune system, particularly in the prenatal period, has far-reaching consequences for health during early childhood, and throughout adult life. One underlying mechanism for the increased levels of allergic responses, secondary to exposure, appears to be an imbalance in the T-helper function caused by exposure to the toxicants. Exposure to environmental endocrine-disrupting chemicals can result in dramatic changes in cytokine production, the activity of the immune system, the overall Th1 and Th2 balance, and in mediators of type 1 hypersensitivity mediators, such as IgE. Passive exposure to tobacco smoke is a common risk factor for wheezing and asthma in children. People living in urban areas and close to roads with a high volume of traffic, and high levels of diesel exhaust fumes, have the highest exposure to environmental compounds, and these people are strongly linked with type 1 hypersensitivity disorders and enhanced Th2 responses. These data are consistent with epidemiological research that has consistently detected increased incidences of allergies and asthma in people living in these locations. During recent decades more than 100,000 new chemicals have been used in common consumer products and are released into the everyday environment. Therefore, in this review, we discuss the environmental effects on allergies of indoor and outside exposure.

The biology of spermatogenesis: the past, present and future

The physiological function of spermatogenesis in Caenorhabditis elegans, Drosophila melanogaster and mammals is to produce spermatozoa (1n, haploid) that contain only half of the genetic material of spermatogonia (2n, diploid). This half number of chromosomes from a spermatozoon will then be reconstituted to become a diploid cell upon fertilization with an egg, which is also haploid. Thus, genetic information from two parental individuals can be passed onto their offspring. Spermatogenesis takes place in the seminiferous epithelium of the seminiferous tubule, the functional unit of the mammalian testis. In mammals, particularly in rodents, the fascinating morphological changes that occur during spermatogenesis involving cellular differentiation and transformation, mitosis, meiosis, germ cell movement, spermiogenesis and spermiation have been well documented from the 1950s through the 1980s. During this time, however, the regulation of, as well as the biochemical and molecular mechanisms underlying these diverse cellular events occurring throughout spermatogenesis, have remained largely unexplored. In the past two decades, important advancements have been made using new biochemical, cell and molecular biology techniques to understand how different genes, proteins and signalling pathways regulate various aspects of spermatogenesis. These include studies on the differentiation of spermatogonia from gonocytes; regulation of spermatogonial stem cells; regulation of spermatogonial mitosis; regulation of meiosis, spermiogenesis and spermiation; role of hormones (e.g. oestrogens, androgens) in spermatogenesis; transcriptional regulation of spermatogenesis; regulation of apoptosis; cell-cell interactions; and the biology of junction dynamics during spermatogenesis. The impact of environmental toxicants on spermatogenesis has also become an urgent issue in the field in light of declining fertility levels in males. Many of these studies have helped investigators to understand important similarities, differences and evolutionary relationships between C. elegans, D. melanogaster and mammals relating to spermatogenesis. In this Special Issue of the Philosophical Transactions of the Royal Society B: Biological Sciences, we have covered many of these areas, and in this Introduction, we highlight the topic of spermatogenesis by examining its past, present and future.

Atherosclerosis-Related Genes, Low-Level Lead Exposure and Age-Related Hearing Loss: The Normative Aging Study

ISEE-0798 Background and Objective: Although age-related hearing loss (ARHL) is one of the leading chronic health conditions experienced by the older adults, little is known about the impact of environmental toxicants and gene-environment interaction. Our recent study has shown associations between cumulative low-level lead exposures and ARHL in a community-based cohort. However, underlying biological mechanisms are still unknown. This study examined whether those associations were modified by genes related to atherosclerosis, including apolipoprotein-E (APOE: rs7412, rs429358, rs405509, rs440446, rs449647, rs769446), lipoprotein lipase (LPL: rs268, rs328, rs1801177), nitric oxide synthase-3 (NOS3: rs1799953, rs1800779), and vascular endothelial growth factor A (VEGFA: rs2010963), given that atherosclerosis which leads to cochlea ischemia and therefore elevate the risk of ARHL may be attributed by lead exposure. Methods: Bone lead levels, markers of cumulative lead exposure, were measured using K-x-ray fluorescence in 563 middle-aged and elderly men in the Normative Aging Study. Pure-tone audiometric examinations were conducted to measure air and bone conduction hearing thresholds. We calculated a pure-tone average (PTA) of thresholds at 500, 1000, 2000, and 4000 Hz. Results: After controlling for potential confounders, an interquartile range increase in tibia lead (14 mg/g) was associated with a 1.7 (95% confidence interval (CI), 0.44, 2.9) dB increase in the air conduction PTA among persons with at least one copy of the minor allele in APOE rs449647, whereas no association was found among persons with homozygous major alleles (−0.85 dB, 95% CI, −2.2, 0.54; P-interaction = 0.005). We also found significant effect modification by APOE rs769446. No effect modification by LPL, NOS3 and VEGFA genetic polymorphisms was found. The results with patella lead and those in the bone conduction PTA were similar but less significant. Conclusion: This study suggests that some SNPs in the promoter region of the APOE gene modify the chronic effects of lead on ARHL.

Impact of Environmental Toxicants on Testicular Function

In recent years, the impact of various environmental toxicants on male reproductive function has received considerable attention, partly fuelled by the reports of falling sperm count and rising reproductive disorders in human population. Environmental toxicants disturb the pro-oxidant/ anti-oxidant balance of the testis resulting in impairment of testicular function. The reactive oxygen species (ROS) and associated oxidative stress has grown up to the point of molecular mechanism responsible for male infertility. Therefore, there is a greater need to look into the reason behind the vulnerability of male reproductive system to ROS. Under physiological conditions, the testicular spermatogenesis and steroidogenesis are associated with production of ROS that makes them more susceptible to oxidative stress. In addition, exposure to toxicants aggravates the production of ROS to greater extent. ROS are involved in regulation of testicular functions within critical levels. The present review outlines the source of ROS, its role in testis and summarizes recent studies on ROSmediated effects of environmental toxicants on testicular function. Testicular spermatogenesis and steroidogenesis are a source of ROS and also a target for their disruptive actions. The role of environmental toxicants in changing testicular ROS levels merits further investigation. Keywords: Oxidative stress, reactive oxygen species, environmental toxicants, spermatogenesis, steroidogenesis, testicular function, Leydig cell, Sertoli cell

Incorporating Environmental Health into Pediatric Medical and Nursing Education

Pediatric medical and nursing education currently lacks the environmental health content necessary to appropriately prepare pediatric health care professionals to prevent, recognize, manage, and treat environmental-exposure–related disease. Leading health institutions have recognized the need for improvements in health professionals’ environmental health education. Parents are seeking answers about the impact of environmental toxicants on their children. Given the biologic, psychological, and social differences between children and adults, there is a need for environmental health education specific to children. The National Environmental Education and Training Foundation, in partnership with the Children’s Environmental Health Network, created two working groups, one with expertise in medical education and one with expertise in nursing education. The working groups reviewed the transition from undergraduate student to professional to assess where in those processes pediatric environmental health could be emphasized. The medical education working group recommended increasing education about children’s environmental health in the medical school curricula, in residency training, and in continuing medical education. The group also recommended the expansion of fellowship training in children’s environmental health. Similarly, the nursing working group recommended increasing children’s environmental health content at the undergraduate, graduate, and continuing nursing education levels. Working groups also identified the key medical and nursing organizations that would be important in leveraging these changes. A concerted effort to prioritize pediatric environmental health by governmental organizations and foundations is essential in providing the resources and expertise to set policy and provide the tools for teaching pediatric environmental health to health care providers.