Current studies indicate that long-term exposure to ambient fine particulate matter (PM₂.₅) is related with global mortality, yet no studies have explored relationships of PM₂.₅ and its species with DNAm PhenoAge acceleration (DNAmPhenoAccel), a new epigenetic biomarker of phenotypic age. We identified which PM₂.₅ species had association with DNAmPhenoAccel in a one-year exposure window in a longitudinal cohort. We collected whole blood samples from 683 elderly men in the Normative Aging Study between 1999 and 2013 (n = 1254 visits). DNAm PhenoAge was calculated using 513 CpGs retrieved from the Illumina Infinium HumanMethylation450 BeadChip. Daily concentrations of PM₂.₅ species were measured at a fixed air-quality monitoring site and one-year moving averages were computed. Linear mixed-effect (LME) regression and Bayesian kernel machine (BKM) regression were used to estimate the associations. The covariates included chronological age, body mass index (BMI), cigarette pack years, smoking status, estimated cell types, batch effects etc. Benjamini-Hochberg false discovery rate at a 5% false positive threshold was used to adjust for multiple comparison. During the study period, the mean DNAm PhenoAge and chronological age in our subjects were 68 and 73 years old, respectively. Using LME model, only lead and calcium were significantly associated with DNAmPhenoAccel. For example, an interquartile range (IQR, 0.0011 μg/m³) increase in lead was associated with a 1.29-year [95% confidence interval (CI): 0.47, 2.11] increase in DNAmPhenoAccel. Using BKM model, we selected PM₂.₅, lead, and silicon to be predictors for DNAmPhenoAccel. A subsequent LME model showed that only lead had significant effect on DNAmPhenoAccel: 1.45-year (95% CI: 0.46, 2.46) increase in DNAmPhenoAccel following an IQR increase in one-year lead. This is the first study that investigates long-term effects of PM₂.₅ components on DNAmPhenoAccel. The results demonstrate that lead and calcium contained in PM₂.₅ was robustly associated with DNAmPhenoAccel.

Numerous recent studies have underlined the crucial players of noncoding RNAs (ncRNAs), i.e., microRNAs(miRNAs), long noncoding RNAs(lncRNAs) and circle RNAs(circRNAs) participating in genotoxic responses induced by a wide variety of environmental genotoxicants consistently. Genotoxic-derived ncRNAs provide us a new epigenetic molecular–ecological network (MEN) insights into the underlying mechanisms regarding genotoxicant exposure and genotoxic effects, which can modify ncRNAs to render them “genotoxic” and inheritable, thus potentially leading to disease risk via epigenetic changes. In fact, the spatial structures of ncRNAs, particularly of secondary and three-dimensional structures, diverse environmental genotoxicants as well as RNA splicing and editing forma dynamic pool of ncRNAs, which constructs a MEN in cells together with their enormous targets and interactions, making biological functions more complicated. We nonetheless suggest that ncRNAs have both beneficial(positive) and harmful(negative) effects, i.e., are “double-edged” in regulating genotoxicant toxic responses. Understanding the “double-edged” effects of ncRNAs is of crucial importance for our further comprehension of the pathogenesis of human diseases induced by environmental toxicants and for the construction of novel prevention and therapy targets. Furthermore, the MEN formed by ncRNAs and their interactions each other as well as downstream targets in the cells is important for considering the active relationships between external agents (environmental toxicants) and inherent genomic ncRNAs, in terms of suppression or promotion (down- or upregulation), and engineered ncRNA therapies can suppress or promote the expression of inherent genomic ncRNAs that are targets of environmental toxicants. Moreover, the MEN would be expected to be would be applied to the mechanistic explanation and risk assessment at whole scene level in environmental genotoxicant exposure. As molecular biology evolves rapidly, the proposed MEN perspective will provide a clearer or more comprehensive holistic view.

Male fertility is progressively declining in many developed countries, but the relationship between male infertility and environmental factors is still unclear.To assess the influence of environmental temperature and air pollution on semen parameters, using a big-data approach.A big data analysis of parameters related to 5131 men, living in a province of Northern Italy and undergoing semen analyses between January 2010 and March 2016 was performed. Ambient temperature was recorded on the day of analysis and the 90 days prior to the analysis and the average value of particulate matter (PM) and NO2 in the year of the test. All data were acquired by geocoding patients residential address. A data warehouse containing 990,904,591 data was generated and analysed by multiple regressions.5573 semen analyses were collected. Both maximum and minimum temperatures registered on the day of collection were inversely related to total sperm number (p < .001), non-progressive motility (NPrM) (p < .005) and normal forms (p < .001). Results were confirmed considering temperature in the 30 and 60 days before collection, but not in the 90 days before collection. Total sperm number was lower in summer/autumn (p < .001) and was inversely related with daylight duration (p < .001). PM10 and PM2.5 were inversely related to PrM (p < .001 and p < .005) and abnormal forms (p < .001).This is the first evaluation of the relationship between male fertility-related parameters and environment using a big-data approach. A seasonal change in semen parameters was found, with a fluctuation related to both temperature and daylight duration. A negative correlation between air pollution and semen quality is suggested. Such seasonal and environmental associations should be considered when assessing changes of male fertility-related parameters over time.

Human studies indicate that phthalate exposure is associated with adverse male reproductive health, and this association may be modified by genetic polymorphisms.We investigated whether apoptosis-related gene polymorphisms modified the associations of phthalate exposure with spermatozoa apoptosis and semen quality.In this Chinese population who sought for semen examination in an infertility clinic, we measured 8 phthalate metabolites in two urine samples to assess the individual's exposure levels. Apoptosis-related gene (Fas, FasL, and caspase3) polymorphisms were performed by real-time PCR. Spermatozoa apoptosis and semen quality parameters were evaluated by Annexin V/PI assay and computer-aided semen analysis, respectively.We found that Fas rs2234767, FasL rs763110, and caspase3 rs12108497 gene polymorphisms significantly modified the associations between urinary phthalate metabolites and spermatozoa apoptosis. For example, urinary monobutyl phthalate (MBP) associated with an increased percentage of Annexin V⁺/PI⁻ spermatozoa of 25.11% (95% CI: 4.08%, 50.53%) were only observed among men with CT/TT genotype of FasL rs763110. In addition, we found that caspase3 rs12108497 gene polymorphisms significantly modified the associations of urinary mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with decreased sperm concentration and sperm count (both p-values for interactions = 0.02).Our results provided the first evidence that apoptosis-related gene polymorphisms might contribute to the effects of phthalate exposure on male reproductive health.

Although in vitro and in vivo laboratory studies have demonstrated androgen and anti-androgen effects on male reproduction from phthalate exposures, human studies still remain inconsistent. Therefore, a case-control study (n = 289) was conducted to evaluate the associations between phthalate exposures, male infertility risks, and changes in metabolomic biomarkers. Regional participants consisted of fertile (n = 150) and infertile (n = 139) males were recruited from Nanjing Medical University’ affiliated hospitals. Seven urinary phthalate metabolites were measured using HPLC-MS/MS. Associations between levels of phthalate metabolites, infertility risks, and infertility-related biomarkers were statistically evaluated. MEHHP, one of the most abundant DEHP oxidative metabolites was significantly lower in cases than in controls (p = 0.039). When using the 1st quartile range as a reference, although statistically insignificant for odds ratios (ORs) of the 2nd, 3rd, and 4th quartiles (OR (95% CI) = 1.50 (0.34–6.48), 0.70 (0.14–3.52) and 0.42 (0.09–2.00), respectively), the MEHHP dose-dependent trend of infertility risk expressed as OR decreased significantly (p = 0.034). More interestingly, most of the phthalate metabolites, including MEHHP, were either positively associated with fertile prevention metabolic biomarkers or negatively associated with fertile hazard ones. Phthalate metabolism, along with their activated infertility-related biomarkers, may contribute to a decreased risk of male infertility at the subjects’ ongoing exposure levels. Our results may be illustrated by the low-dose related androgen effect of phthalates and can improve our understanding of the controversial epidemiological results on this issue.

Africa's economy is growing faster than any other continent and it has been estimated that the middle class in Africa now exceeds 350 million people. This has meant a parallel increase in the importation of consumer goods and in the implementation of communication and information technologies (ICT), but also in the generation of large quantities of e-waste. However, inadequate infrastructure development remains a major constraint to the continent's economic growth and these highly toxic residues are not always adequately managed. Few studies have been conducted to date assessing the possible association between socioeconomic development factors, including e-waste generation, and blood levels of inorganic elements in African population. To disclose the role of geographical, anthropogenic, and socioeconomic development determinants on the blood levels of Ag, Al, As, Be, Cd, Co, Cr, Hg, Ni, Pb, Sb, and V —all of them frequently found in e-waste—, an immigrant population-based study was made including a total of 245 subjects from 16 countries recently arrived to the Canary Islands (Spain). Women presented higher levels of blood elements than men, and Northern Africans (Moroccans) were the most contaminated. People from low-income countries exhibited significantly lower blood levels of inorganic elements than those from middle-income countries. We found a significant association between the use of motor vehicles and the implementation of information and communication technologies (ICT) and the level of contamination. Immigrants from the countries with a high volume of imports of second-hand electronic equipment, telephone and internet use had higher levels of inorganic elements. In general terms, the higher level of economic development the higher the blood levels of inorganic pollutants, suggesting that the economic development of Africa, in parallel to e-waste generation and the existence of informal recycling sites, have directly affected the level of contamination of the population of the continent.

This study aimed to investigate the relationships between environmental exposure to metals/metalloids and semen quality, sperm apoptosis and DNA integrity using the metal/metalloids levels in seminal plasma as biomarkers. We determined 18 metals/metalloids in seminal plasma using an inductively coupled plasma-mass spectrometry among 746 men recruited from a reproductive medicine center. Associations of these metals/metalloids with semen quality (n = 746), sperm apoptosis (n = 331) and DNA integrity (n = 404) were evaluated using multivariate linear and logistic regression models. After accounting for multiple comparisons and confounders, seminal plasma arsenic (As) quartiles were negatively associated with progressive and total sperm motility using multivariable linear regression analysis, which were in accordance with the trends for increased odds ratios (ORs) for below-reference semen quality parameters in the logistic models. We also found inverse correlations between cadmium (Cd) quartiles and progressive and total sperm motility, whereas positive correlations between zinc (Zn) quartiles and sperm concentration, between copper (Cu) and As quartiles and the percentage of tail DNA, between As and selenium (Se) quartiles and tail extent and tail distributed moment, and between tin (Sn) categories and the percentage of necrotic spermatozoa (all Ptrend<0.05). These relationships remained after the simultaneous consideration of various elements. Our results indicate that environmental exposure to As, Cd, Cu, Se and Sn may impair male reproductive health, whereas Zn may be beneficial to sperm concentration.

Few prior cohort studies exist in developing countries examining the association of ambient particulate matter (PM) with mortality. We examined the association of particulate air pollution with mortality in a prospective cohort study of 71,431 middle-aged Chinese men. Baseline data were obtained during 1990–1991. The follow-up evaluation was completed in January, 2006. Annual average PM exposure between 1990 and 2005, including TSP and PM10, were estimated by linking fixed-site monitoring data with residential communities. We found significant associations between PM10 and mortality from cardiopulmonary diseases; each 10 μg/m3 PM10 was associated with a 1.6% (95%CI: 0.7%, 2.6%), 1.8% (95%CI: 0.8%, 2.9%) and 1.7% (95%CI: 0.3%, 3.2%) increased risk of total, cardiovascular and respiratory mortality, respectively. For TSP, we observed significant associations only for cardiovascular morality. These data contribute to the scientific literature on long-term effects of particulate air pollution for high exposure settings typical in developing countries.

As a crucial factor in male reproduction, androgens may represent an intermediate biological mechanism linking metal exposure with effects on semen quality. This study aimed to investigate the association between metal exposure and semen quality, and to assess the mediating role of seminal androgens between metal exposure and semen quality. We investigated the presence of 10 metals in semen and assessed their effect on semen quality in 1136 men recruited from a hospital in Shenzhen, China. Of these, 464 subjects were randomly selected for 4 androgens detection in semen. Cross-sectional associations between single/multiple metals, androgen levels and semen quality were explored by multivariable linear regressions. Mediation analysis was performed to detect the role of seminal androgens on the association between metal exposure and semen quality. Seminal selenium and iron were positively associated with both sperm concentration and total sperm count. Negative associations were observed between both manganese and zinc and sperm concentration, molybdenum and total sperm count, copper and sperm motility. Furthermore, we found significant dose-dependent relationships between both iron and selenium levels and dihydrotestosterone (DHT), arsenic levels and testosterone, as well as zinc and dehydroepiandrosterone. Mediation analysis indicated that higher seminal iron and selenium were associated with an increasing sperm concentration after controlling for DHT, with 10.32% and 12.89% of these associations were mediated by DHT, respectively. A similar mediation effect of DHT was observed in the associations between iron and selenium levels and total sperm count (13.39% and 21.57% mediation, respectively). Our findings suggested that the presence of selenium and iron in semen was beneficial to sperm concentration and total count. Seminal manganese, zinc, molybdenum and copper may be associated with reduced semen quality. The associations between seminal selenium and iron and sperm concentration and total count were partially explained by the concomitant variation of seminal DHT.