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Abstract Background Airborne pollution particles have been shown to translocate from the mother’s lung to the fetal circulation, but their distribution and internal placental-fetal tissue load remain poorly explored. Here, we investigated the placental-fetal load and distribution of diesel engine exhaust particles during gestation under controlled exposure conditions using a pregnant rabbit model. Pregnant dams were exposed by nose-only inhalation to either clean air (controls) or diluted and filtered diesel engine exhaust (1 mg/m3) for 2 h/day, 5 days/week, from gestational day (GD) 3 to GD27. At GD28, placental and fetal tissues (i.e., heart, kidney, liver, lung and gonads) were collected for biometry and to study the presence of carbon particles (CPs) using white light generation by carbonaceous particles under femtosecond pulsed laser illumination. Results CPs were detected in the placenta, fetal heart, kidney, liver, lung and gonads in significantly higher amounts in exposed rabbits compared with controls. Through multiple factor analysis, we were able to discriminate the diesel engine exposed pregnant rabbits from the control group taking all variables related to fetoplacental biometry and CP load into consideration. Our findings did not reveal a sex effect, yet a potential interaction effect might be present between exposure and fetal sex. Conclusions The results confirmed the translocation of maternally inhaled CPs from diesel engine exhaust to the placenta which could be detected in fetal organs during late-stage pregnancy. The exposed can be clearly discriminated from the control group with respect to fetoplacental biometry and CP load. The differential particle load in the fetal organs may contribute to the effects on fetoplacental biometry and to the malprogramming of the fetal phenotype with long-term effects later in life.

Background: Ultrafine particles, including black carbon (BC), can reach the systemic circulation and therefore may distribute to distant organs upon inhalation. The kidneys may be particularly vulnerable to the adverse effects of BC exposure due to their filtration function. Objectives: We hypothesized that BC particles reach the kidneys via the systemic circulation, where the particles may reside in structural components of kidney tissue and impair kidney function. Methods: In kidney biopsies from 25 transplant patients, we visualized BC particles using white light generation under femtosecond-pulsed illumination. The presence of urinary kidney injury molecule-1 (KIM-1) and cystatin c (CysC) were evaluated with ELISA. We assessed the association between internal and external exposure matrices and urinary biomarkers using Pearson correlation and linear regression models. Results: BC particles could be identified in all biopsy samples with a geometric mean (5th, 95th percentile) of 1.80 × 103 (3.65 × 102, 7.50 × 103) particles/mm3 kidney tissue, predominantly observed in the interstitium (100 %) and tubules (80 %), followed by the blood vessels and capillaries (40 %), and the glomerulus (24 %). Independent from covariates and potential confounders, we found that each 10 % higher tissue BC load resulted in 8.24 % (p = 0.03) higher urinary KIM-1. In addition, residential proximity to a major road was inversely associated with urinary CysC (+10 % distance: −4.68 %; p = 0.01) and KIM-1 (+10 % distance: −3.99 %; p

Abstract Background Ambient fine particulate matter (PM < 2.5 μm, PM2.5) is gaining increasing attention as an environmental risk factor for health. The kidneys are considered a particularly vulnerable target to the toxic effects that PM2.5 exerts. Alteration of kidney function may lead to a disrupted homeostasis, affecting disparate tissues in the body. This review intends to summarize all relevant knowledge published between January 2000 and December 2021 on the effects of ambient PM2.5 and the adverse effects on kidney function in adults (≥ 18 years). Results and Discussion Studies published in peer-reviewed journals, written in English, regarding the effects of PM2.5 on kidney function and the development and/or exacerbation of kidney disease(s) were included. Of the 587 nonduplicate studies evaluated, 40 were included, comprising of studies on healthy or diagnosed with pre-existing disease (sub)populations. Most of the studies were cohort studies (n = 27), followed by 10 cross-sectional, 1 ecological and 2 time-series studies. One longitudinal study was considered intermediate risk of bias, the other included studies were considered low risk of bias. A large portion of the studies (n = 36) showed that PM2.5 exposure worsened kidney outcome(s) investigated; however, some studies show contradictory results. Measurement of the estimated glomerular filtration rate, for instance, was found to be positively associated (n = 8) as well as negatively associated (n = 4) with PM2.5. Limitations and Conclusion The main limitations of the included studies include residual confounding (e.g., smoking) and lack of individual exposure levels. The majority of included studies focused on specific subpopulations, which may limit generalizability. Evidence of the detrimental effects that ambient PM2.5 may exert on kidney function is emerging. However, further investigations are required to determine how and to what extent air pollution, specifically PM2.5, exerts adverse effects on the kidney and alters its function. Registration The systematic review protocol was submitted and published by the International Prospective Register of Systematic Reviews (PROSPERO; CRD42020175615 ).

Abstract Background Pregnant women and developing fetuses comprise a particularly vulnerable population as multiple studies have shown associations between prenatal air pollution exposure and adverse pregnancy outcomes. However, the mechanisms underlying the observed developmental toxicity are mostly unknown, in particular, if pollution particles can cross the human placenta to reach the fetal circulation. Results Here, we investigated the accumulation and translocation of diesel exhaust particles (DEPs), as a model particle for combustion-derived pollution, in human perfused placentae using label-free detection by femtosecond pulsed laser illumination. The results do not reveal a significant particle transfer across term placentae within 6 h of perfusion. However, DEPs accumulate in placental tissue, especially in the syncytiotrophoblast layer that mediates a wealth of essential functions to support and maintain a successful pregnancy. Furthermore, DEPs are found in placental macrophages and fetal endothelial cells, showing that some particles can overcome the syncytiotrophoblasts to reach the fetal capillaries. Few particles are also observed inside fetal microvessels. Conclusions Overall, we show that DEPs accumulate in key cell types of the placental tissue and can cross the human placenta, although in limited amounts. These findings are crucial for risk assessment and protection of pregnant women and highlight the urgent need for further research on the direct and indirect placenta-mediated developmental toxicity of ambient particulates.

Abstract Background In vitro models are widely used in nanotoxicology. In these assays, a careful documentation of the fraction of nanomaterials that reaches the cells, i.e. the in vitro delivered dose, is a critical element for the interpretation of the data. The in vitro delivered dose can be measured by quantifying the amount of material in contact with the cells, or can be estimated by applying particokinetic models. For carbon nanotubes (CNTs), the determination of the in vitro delivered dose is not evident because their quantification in biological matrices is difficult, and particokinetic models are not adapted to high aspect ratio materials. Here, we applied a rapid and direct approach, based on femtosecond pulsed laser microscopy (FPLM), to assess the in vitro delivered dose of multi-walled CNTs (MWCNTs). Methods and results We incubated mouse lung fibroblasts (MLg) and differentiated human monocytic cells (THP-1) in 96-well plates for 24 h with a set of different MWCNTs. The cytotoxic response to the MWCNTs was evaluated using the WST-1 assay in both cell lines, and the pro-inflammatory response was determined by measuring the release of IL-1β by THP-1 cells. Contrasting cell responses were observed across the MWCNTs. The sedimentation rate of the different MWCNTs was assessed by monitoring turbidity decay with time in cell culture medium. These turbidity measurements revealed some differences among the MWCNT samples which, however, did not parallel the contrasting cell responses. FPLM measurements in cell culture wells revealed that the in vitro delivered MWCNT dose did not parallel sedimentation data, and suggested that cultured cells contributed to set up the delivered dose. The FPLM data allowed, for each MWCNT sample, an adjustment of the measured cytotoxicity and IL-1β responses to the delivered doses. This adjusted in vitro activity led to another toxicity ranking of the MWCNT samples as compared to the unadjusted activities. In macrophages, this adjusted ranking was consistent with existing knowledge on the impact of surface MWCNT functionalization on cytotoxicity, and might better reflect the intrinsic activity of the MWCNT samples. Conclusion The present study further highlights the need to estimate the in vitro delivered dose in cell culture experiments with nanomaterials. The FPLM measurement of the in vitro delivered dose of MWCNTs can enrich experimental results, and may refine our understanding of their interactions with cells.

Abstract Fetal development is a crucial window of susceptibility in which exposure may lead to detrimental health outcomes at birth and later in life. The placenta serves as a gatekeeper between mother and fetus. Knowledge regarding the barrier capacity of the placenta for nanoparticles is limited, mostly due to technical obstacles and ethical issues. We systematically summarize and discuss the current evidence and define knowledge gaps concerning the maternal-fetal transport and fetoplacental accumulation of (ultra)fine particles and nanoparticles. We included 73 studies on placental translocation of particles, of which 21 in vitro/ex vivo studies, 50 animal studies, and 2 human studies on transplacental particle transfer. This systematic review shows that (i) (ultra)fine particles and engineered nanoparticles can bypass the placenta and reach fetal units as observed for all the applied models irrespective of the species origin (i.e., rodent, rabbit, or human) or the complexity (i.e., in vitro, ex vivo, or in vivo), (ii) particle size, particle material, dose, particle dissolution, gestational stage of the model, and surface composition influence maternal-fetal translocation, and (iii) no simple, standardized method for nanoparticle detection and/or quantification in biological matrices is available to date. Existing evidence, research gaps, and perspectives of maternal-fetal particle transfer are highlighted.

Abstract Background Particulate matter exposure during in utero life may entail adverse health outcomes later in life. The microvasculature undergoes extensive, organ-specific prenatal maturation. A growing body of evidence shows that cardiovascular disease in adulthood is rooted in a dysfunctional fetal and perinatal development, in particular that of the microcirculation. We investigate whether prenatal or postnatal exposure to PM2.5 (particulate matter with a diameter ≤ 2.5 μm) or NO2 is related to microvascular traits in children between the age of four and six. Methods We measured the retinal microvascular diameters, the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE), and the vessel curvature by means of the tortuosity index (TI) in young children (mean [SD] age 4.6 [0.4] years), followed longitudinally within the ENVIRONAGE birth cohort. We modeled daily prenatal and postnatal PM2.5 and NO2 exposure levels for each participant’s home address using a high-resolution spatiotemporal model. Results An interquartile range (IQR) increase in PM2.5 exposure during the entire pregnancy was associated with a 3.85-μm (95% CI, 0.10 to 7.60; p = 0.04) widening of the CRVE and a 2.87-μm (95% CI, 0.12 to 5.62; p = 0.04) widening of the CRAE. For prenatal NO2 exposure, an IQR increase was found to widen the CRVE with 4.03 μm (95% CI, 0.44 to 7.63; p = 0.03) and the CRAE with 2.92 μm (95% CI, 0.29 to 5.56; p = 0.03). Furthermore, a higher TI score was associated with higher prenatal NO2 exposure. We observed a postnatal effect of short-term PM2.5 exposure on the CRAE and a childhood NO2 exposure effect on both the CRVE and CRAE. Conclusions Our results link prenatal and postnatal air pollution exposure with changes in a child’s microvascular traits as a fundamental novel mechanism to explain the developmental origin of cardiovascular disease.

Exposure to air pollution during pregnancy has been associated with impaired birth outcomes. Here, Bové et al. report evidence of black carbon particle deposition on the fetal side of human placentae, including at early stages of pregnancy, suggesting air pollution could affect birth outcome through direct effects on the fetus.

Introduction: Inhalation of asbestos induces lung cancer via different cellular mechanisms. Together with the increased production of carbon nanotubes (CNTs) grows the concern about adverse effects on the lungs given the similarities with asbestos. While it has been established that CNT and asbestos induce epigenetic alterations, it is currently not known whether alterations at epigenetic level remain stable after withdrawal of the exposure. Identification of DNA methylation changes after a low dose of CNT and asbestos exposure and recovery can be useful to determine the fibre/particle toxicity and adverse outcome. Methods: Human bronchial epithelial cells (16HBE) were treated with a low and non-cytotoxic dose (0.25 µg/ml) of multi-walled carbon nanotubes (MWCNTs-NM400) or single-walled carbon nanotubes (SWCNTs-SRM2483) and 0.05 µg/ml amosite (brown) asbestos for the course of four weeks (sub-chronic exposure). After this treatment, the cells were further incubated (without particle/fibre) for two weeks, allowing recovery from the exposure (recovery period). Nuclear depositions of the CNTs were assessed using femtosecond pulsed laser microscopy in a label-free manner. DNA methylation alterations were analysed using microarrays that assess more than 850 thousand CpG sites in the whole genome. Results: At non-cytotoxic doses, CNTs were noted to be incorporated with in the nucleus after a four weeks period. Exposure to MWCNTs induced a single hypomethylation at a CpG site and gene promoter region. No change in DNA methylation was observed after the recovery period for MWCNTs. Exposure to SWCNTs or amosite induced hypermethylation at CpG sites after sub-chronic exposure which may involve in ‘transcription factor activity’ and ‘sequence-specific DNA binding’ gene ontologies. After the recovery period, hypermethylation and hypomethylation were noted for both SWCNTs and amosite. Hippocalcinlike 1 (HPCAL1), protease serine 3 (PRSS3), kallikrein-related peptidase 3 (KLK3), kruppel like factor 3 (KLF3) genes were hypermethylated at different time points in either SWCNT-exposed or amosite-exposed cells. Conclusion: These results suggest that the specific SWCNT (SRM2483) and amosite fibres studied induce hypo- or hypermethylation on CpG sites in DNA after very low-dose exposure and recovery period. This effect was not seen for the studied MWCNT (NM400). Keywords: Carbon nanotube, Asbestos, Epigenetics, DNA methylation

Abstract Background The continuously growing human exposure to combustion-derived particles (CDPs) drives in depth investigation of the involved complex toxicological mechanisms of those particles. The current study evaluated the hypothesis that CDPs could affect cell-induced remodeling of the extracellular matrix due to their underlying toxicological mechanisms. The effects of two ultrafine and one fine form of CDPs on human lung fibroblasts (MRC-5 cell line) were investigated, both in 2D cell culture and in 3D collagen type I hydrogels. A multi-parametric analysis was employed. Results In vitro dynamic 3D analysis of collagen matrices showed that matrix displacement fields induced by human lung fibroblasts are disturbed when exposed to carbonaceous particles, resulting in inhibition of matrix remodeling. In depth analysis using general toxicological assays revealed that a plausible explanation comprises a cascade of numerous detrimental effects evoked by the carbon particles, including oxidative stress, mitochondrial damage and energy storage depletion. Also, ultrafine particles revealed stronger toxicological and inhibitory effects compared to their larger counterparts. The inhibitory effects can be almost fully restored when treating the impaired cells with antioxidants like vitamin C. Conclusions The unraveled in vitro pathway, by which ultrafine particles alter the fibroblasts’ vital role of matrix remodeling, extends our knowledge about the contribution of these biologically active particles in impaired lung tissue repair mechanisms, and development and exacerbation of chronic lung diseases. The new insights may even pave the way to precautionary actions. The results provide justification for toxicological assessments to include mechanism-linked assays besides the traditional in vitro toxicological screening assays.

Abstract Background Carbon load in airway macrophages (AM) has been proposed as an internal marker to assess long-term exposure to combustion-derived pollutant particles. However, it is not known how this biomarker is affected by changes in exposure. We studied the clearance kinetics of black carbon (BC) in AM, obtained by sputum induction, in a one-year panel study. Methods AM BC was measured 8 times with 6 weeks intervals in healthy young subjects: 15 long-term residents in Leuven, Belgium (BE, mean annual PM10 20–30 μg/m3) and 30 newcomers having arrived recently ( 50 μg/m3) in low and middle-income countries (LMIC, n = 15), or from low to moderately polluted cities in high-income countries (HIC, n = 15). The median and 90th percentile values of AM BC were quantified by image analysis of 25 macrophages per sputum sample; the carbonaceous nature of the black inclusions in AM was verified by Femtosecond Pulsed Laser Microscopy in 30 macrophages. We used a Bayesian hierarchical single-exponential decay model to describe the evolution of AM BC. Results In the LMIC group, the mean (95% credible interval) initial quantity (R0) of median AM BC [1.122 (0.750–1.509) μm2] was higher than in the HIC group [0.387 (0.168–0.613) μm2] and BE group [0.275 (0.147–0.404) μm2]. Median AM BC content decreased in the LMIC group (decay constant 0.013 μm2/day), but remained stable over one year in the other two groups. In the LMIC group, clearance half-lives of 53 (30–99) and 116 (63–231) days, were calculated for median and 90th percentile AM BC, respectively. Conclusions In this real-life study of an international panel of healthy young subjects, we demonstrated that carbon load in airway macrophages obtained by induced sputum reflects past long-term exposure to particulate air pollution. Values of AM BC do not change over one year when exposure remains stable, but AM BC decreases upon moving from high to moderate exposure, with average half-lives of 53 and 116 days depending on the carbon load.

Abstract Background Subtle DNA methylation alterations mediated by carbon nanotubes (CNTs) exposure might contribute to pathogenesis and disease susceptibility. It is known that both multi-walled carbon nanotubes (MWCNTs) and single-walled carbon nanotubes (SWCNTs) interact with nucleus. Such, nuclear-CNT interaction may affect the DNA methylation effects. In order to understand the epigenetic toxicity, in particular DNA methylation alterations, of SWCNTs and short MWCNTs, we performed global/genome-wide, gene-specific DNA methylation and RNA-expression analyses after exposing human bronchial epithelial cells (16HBE14o- cell line). In addition, the presence of CNTs on/in the cell nucleus was evaluated in a label-free way using femtosecond pulsed laser microscopy. Results Generally, a higher number of SWCNTs, compared to MWCNTs, was deposited at both the cellular and nuclear level after exposure. Nonetheless, both CNT types were in physical contact with the nuclei. While particle type dependency was noticed for the identified genome-wide and gene-specific alterations, no global DNA methylation alteration on 5-methylcytosine (5-mC) sites was observed for both CNTs. After exposure to MWCNTs, 2398 genes were hypomethylated (at gene promoters), and after exposure to SWCNTs, 589 CpG sites (located on 501 genes) were either hypo- (N = 493 CpG sites) or hypermethylated (N = 96 CpG sites). Cells exposed to MWCNTs exhibited a better correlation between gene promoter methylation and gene expression alterations. Differentially methylated and expressed genes induced changes (MWCNTs > SWCNTs) at different cellular pathways, such as p53 signalling, DNA damage repair and cell cycle. On the other hand, SWCNT exposure showed hypermethylation on functionally important genes, such as SKI proto-oncogene (SKI), glutathione S-transferase pi 1 (GTSP1) and shroom family member 2 (SHROOM2) and neurofibromatosis type I (NF1), which the latter is both hypermethylated and downregulated. Conclusion After exposure to both types of CNTs, epigenetic alterations may contribute to toxic or repair response. Moreover, our results suggest that the observed differences in the epigenetic response depend on particle type and differential CNT-nucleus interactions.

The aerial surfaces of plants harbor diverse communities of microorganisms. The rising awareness concerning the potential roles of these phyllosphere microbiota for airborne pollutant remediation and plant growth promotion, advocates for a better understanding of their community structure and dynamics in urban ecosystems. Here, we characterized the epiphytic microbial communities on leaves of Platanus × hispanica trees in the city centre of Hasselt (Belgium), and the nearby forest area of Bokrijk, Genk (Belgium). We compared the influences of season, site, and air pollutants concentration variations on the tree’s phyllosphere microbiome by determining the intra- and inter-individual variation in leaf bacterial communities. High-throughput amplicon sequencing of the 16S rRNA gene revealed large variation in the bacterial community structure and diversity throughout the years but also allowed to discriminate an environment effect on community assembly. Partial drivers for this environment effect on composition can be correlated with the huge differences in ultrafine particulate matter (UFP) and black carbon on the leaves. A change in bacterial community composition was noted for trees growing in the city center compared to the natural site, and also more human-associated genera were found colonizing the leaves from the city center. These integrated results offer an original and first insight in the Platanus phyllomicrobiota, which can offer new opportunities to use phyllosphere microorganisms to enhance air pollution degradation.