Table 1.
Cellular effects associated to air pollution exposure during pregnancy.
| Reference | Study design | Exhaust/non-exhaust | Pollutants associate to observed effects | Exposure concentration/time associate to observed effects | Observed effects | Statistics of associations |
|---|---|---|---|---|---|---|
| Smith et al. (53) | Retrospective population-based cohort study. 540 365 singleton term live births |
exhaust non-exhaust |
PM2.5traffic exhaust from London, UK PM2.5traffic non-exhaust from London, UK |
>13.8 μg/m3 | Residential exposure to PM2.5 traffic exhaust during pregnancy is directly attributable to 3% of term LBW cases in London By analogy, the authors hypothesize that the mechanisms involved may include, oxidative stress, changes in oxygen or nutrition transfer, placental mitochondrial damage, or endocrine disruption |
Odds ratio (95% CI) PM2.5traffic exhaust 1.04 (1.01 to 1.07) |
| Zhou et al. (19) | Cohort of 1060 mother-child pairs recruited between April 2016 and December 2018 Sample: maternal blood |
mixture | PM2.5 from Shanghai, China | Mean 37.74 μg/m3 | PM2.5 inorganic constituents, such as Al, Si, K, Mn, and Zn, appear to be responsible for increase in maternal TSH and decreased in maternal serum free thyroxine (fT4) that lead changes in fetal growth measures | % change (95% CI) Maternal TSH: increases of 12.75% (1.01%, 24.61%) Maternal fT4: decreases of 5.82% (8.61%, -2.96%) |
| Liu et al. (84) | Cell line: Epithelial alveolar cells (A549) | mixture | PM from urban dust (SRM1649b) purchased from NIST (MD, USA) | 100 μg/mL/24 h | Increases the expression of ROS, ICAM-1 and the production of interleukin-6 (IL-6) | n.a |
| Bové et al. (17) | 20 mothers Sample: Placenta |
exhaust | BC from Belgium | annual means ranging from 0.63 to 2.42 µg per m3/entire pregnancy | The presence of particles from air pollution within the placenta of all participating mothers was evidenced. The number of placental particles per mm3 was positively associated with the mothers’ residential exposure to BC during pregnancy | Increases (95% CI) Increased placental BC load associated with increased residential BC exposure:+0.45 × 104 per mm3 (0.11 × 104 to 0.80 × 104) |
| Li et al. (85) | Cell line: HAEC | exhaust | Diesel exhausted particles, collected from a 1998 Kenworth truck | 50 μg/ml/4 h | Down-regulation of Zonular Occludin-1 (ZO-1) leading an increase in permeability | n.a |
| Le et al. (86) | Primary cell culture: HUVEC | mixture | PM2.5, China | 10 μg/mL/12 h | Increases mRNA and protein levels of TLR2, TLR4 Increase mRNA expression of IL-1 β, and IL-6 |
n.a |
| Su et al. (87) | Primary cell culture: HUVEC | mixture | PM2.5 from Taiyuan, China | 10 μg/cm2/6 h | Induced significant structural and functional damage in mitochondria and lysosomes PM2.5 internalization is mediated by clathrin and caveolin |
n.a |
| Ma et al. (88) | Cell line: MHC | mixture | PM2.5 from Langfan, China | 500 μg/mL/48 h | PM2.5 induces Endothelial–Mesenchymal Transition (EndMT) by activating the TGF-β1/Smad3/p-Smad3 pathway. |
n.a |
| Xu et al. (117) | Primary cell culture: HUVEC | mixture | PM2.5 from Wuhan, China | 12.5 μg/mL/24 h | The activation of ERKs, p38 kinase and JNKs mediates the induction of AT1R | n.a |
| Xu et al. (89) | Primary cell culture: HUVEC | mixture | PM2.5 from Wuhan, China | 12.5 μg/mL/24 h | Induction of endoplasmic reticulum stress leading to HIF1α transactivation, which in turn mediates endothelial dysfunction by upregulation of components of the ACE/ANGII/AT1R axis in the endothelial cell | n.a |
| Wauters et al. (90) | 12 healthy male volunteers | exhaust | PM2.5 from diesel exhaust from PSA DW10 engine (common in Europe) | 300 μg/m3/120 minutes at rest | The acetylcholine/sodium nitroprusside vasodilation ratio decreased after polluted air decreased significantly and was inversely correlated to the total amount of PM2.5 inhaled. Impairments in microvascular function measured by NO bioavailability decrease and ROS increase. |
Spearman correlation coefficient (r=−0.55, P<0.01) |
| Calderón-Garcidueñas et al. (91) | Healthy children, 6–13 years of age | mixture | PM2.5 from Mexico City | 4000 μg/m3/h/7-day cumulative outdoor dose | The increase in circulating ET-1 concentrations showed a positive association with the number of daily hours outdoors. An increase in mean pulmonary arterial pressure (PAPM) was observed. |
Pearson’s correlation (r = 0.31, p = 0.012) |
| Finch et al. (118) | Young, healthy nonsmokers | mixture | PM2.5 from Utah, USA | 50 μg/m3/24 h | Negative association between acute exposure to PM2.5 and circulating levels of ET-1 | Beta (95% CI) ambient PM2.5 and blood ET-1: β −0.773 (−1.18, −0.365) |
| Grevendonk et al. (92) | 293 mother-newborn pairs | mixture | PM2.5 and PM10, from Belgium | PM2.5, 16.6 μg/m3/entire pregnancy PM10, 21.4 μg/m3/entire pregnancy |
PM10 and PM2.5 exposure during the entire pregnancy were positively correlated with mitochondrial 8-OHdG levels in maternal blood | % change (95% CI) PM2.5 exposure: increase of mitochondrial 8-OHdG levels in maternal blood 13.9% (0.4 to 29.4%) PM10 exposure: increase of mitochondrial 8-OHdG levels in maternal blood 18.3% (5.6 to 33.4%) |
| Saenen et al. (93) | 502 mother-newborn pairs | mixture | PM2.5 and BC from Belgium | PM2.5, 15.8 μg/m3/first trimester of pregnancy PM2.5, 15.3 μg/m3/second trimester of pregnancy BC, 0,90 μg/m3/first trimester of pregnancy |
Placental nitrosative stress marker, 3-nitrotyrosine (3-NTp) were positively associated with PM2.5 and BC exposure levels during gestation | % change (95% CI) Placental 3-NTp increases by each gestational time window of exposure PM2.5 first trimestre exposure: 29.0%, (4.9, 58.6); second trimestre exposure: 39.3%, (12.3, 72.7) BC first trimester exposure: 23.6%, (4.4, 46.4) |
| Dong et al. (40) | 64 pregnant women | exhaust | HMWPAHs compounds, mainly from the incomplete combustion or pyrolysis of biomass from Kunming, China | n.a. | The low accumulation of PAHs inside the placenta was related to pregnancy complications and increased levels of PAHs in maternal and umbilical cord blood. | n.a. |
| Familari et al. (94) | Cell line: HTR-8/SVneo cells | mixture | PM2.5 from Malmö, Swedenand PM10 from Prague, Czech Republic |
500-5000 ng/mL/48h | Decreased hCGβ secretion and increased IL-6 secretion | n.a. |
| Nääv et al. (95) | Cell line: HTR-8/SVneo cells | mixture | PM2.5 from Malmö, Sweden | 500 ng/mL/48h | Cytotoxicity, increase in progesterone and IL-6 secretion | n.a. |
| Qin et al. (96) | Cell line: HTR-8/SVneo cells | mixture | PM2.5 from Tianjin City, China | 120 μg/mL/24 and 48 h | Inhibition of migration and invasion, DNA damage and cell cycle G2/M arrest Higher ROS generation and increasing TIMP1 and TIMP2 expression | n.a. |
| Agarwal et al. (39) | 84 pregnant women Sample: Placental tissue |
exhaust | PAHs from Agra, India |
LMWPAHs 2.047 μg/L/n.a HMWPAHs 3.016 μg/L/n.a total PAHs 5.064 μg/L/n.a |
Negative correlation was observed between low, high, total PAHs and GSH levels, both in placental tissue. The level of MDA was significantly high in placental tissue and was associated with total PAHs levels. The observed increase in MDA and decrease in GSH suggests an imbalance in oxidant homeostasis |
Pearson’s correlation GSH and LMWPAHs (r = -0.306, p < 0.01), HMWPAHs (r = -0.441, p < 0.001), and TPAHs (r = -0.388, p < 0.001) MDA and total PAHs (r = 0.27, p = 0.0128). |
| Herbstman et al. (97) | 164 pregnant women maternal Sample: umbilical cord blood leukocytes |
exhaust | PAHs from New York City, USA | PAHs, including pyrene, 5.314 ng/m3/ third trimester | Maternal exposure to PAHs decreased cord blood global methylation however, B[a]P–DNA adduct formation was associated with higher global DNA methylation in umbilical cord white blood cells | β-values (95% CI) Global methylation in umbilical cord blood and prenatal PAHs exposure: β = –0.11; (–0.21, 0.00) Odds ratio (95% CI) BaP-DNA adducts in umbilical cord blood and increased levels of genomic methylation 2,35; (1,35, 4,09) |
| Al-Saleh et al. (38) | 1578 women Sample: maternal urine and placental tissue |
exhaust | PAHs from Al-Kharj, Saudi Arabia | PAHs n.a. | High levels of BaP in the placenta were associated with decreased placental thickness and decreased cord length. A positive relationship was found between the levels of 8-OHdG and 1-HP in maternal urine. | β-values (P) Placental thickness −0.071 (0.018) Cord length −0.074 (0.013) β Weight (P) 8-OHdG and 1-HP 0.303 (<0.001) |
| van Drooge et al. (98) | Cell line: JEG-3 cells | mixture | Rural and urban PM1 from Barcelona, Spain | PM1 11 and 12 m3 eqAir/mL/24 h | PAHs from PM1 emitted by biomass burning induce cytotoxicity and inhibition of aromatase activity in JEG-3 cells | n.a |
| Karttunen et al. (43) | 12 uncomplicate pregnancies Tissue: Placenta |
exhaust | 3 H-BP (Amersham Biosciences) | 0.1 – 1 μM BP/15 min – 6 h | Transfer of BP from the placental maternal side to the fetal circulation was confirmed by placental perfusion experiments BPDE–DNA adducts were found in placental tissue after the perfusion with 1 μM BP |
n.a |
| Wang et al. (99) | Cell line: Swan71 cells | exhaust | Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) | 0.25 – 4 μM BPDE/24 h | BPDE reduces hCG secretion and also prevents trophoblast cell invasion in a dose-dependent manner BPDE induces apoptosis in a dose-dependent manner and induced mitochondrial damage BPDE increase in ROS, MDA, and inflammation, and decrease in SOD |
n.a |
| Wang et al. (100) | Cell line: JEG-3 cells | mixture | PM2.5 from Shanxi, China | 1 - 10 μg/mL/48 – 96 h | JEG-3 cells exposure to PM2.5 increased hCG levels at both 24 h and 48 h Cell proliferation decreased at 24 h |
n.a |
| Wakx et al. (101) | 3 healthy mothers with uncomplicated pregnancies Primary cell culture: Ex vivo trophoblasts cells Cell line: JEG-3 |
exhaust | B[a]P (Sigma, Saint-Quentin Fallavier, France) | 0.1 – 10 μM/72 h | In ex vivo placental cells, incubation with 10 μM B[a]P for 48 h did not cause loss of cell viability or DNA fragmentation. JEG-3 cells exposed to 10 μM B[a]P for 72 h leads to cell cycle arrest (G2/M phase) and a significant decrease in cell proliferation and DNA damage. |
|
| Pidoux et al. (102) | Tissue: Placenta | n.a | [14C]-formaldehyde (50 mCi/mmol, Perkin-Elmer) | 100 μM | Accumulation of formaldehyde in the placenta and the fetal compartments and hormonal dysfunction | n.a |
| Shen et al. (103) | HUVECs | n.a | Cooking Oil Fumes-derived PM2.5 | 25, 50, 100, 150, and 200 μg/mL | Reduce cells viability, overproduction of ROS, activation of NLRP3 and IL-1β inflammasome, and inhibition of VEGF expression which directly affects angiogenesis | n.a |
UK, United Kingdom; LBW, Low birth weight; TSH, thyroid-stimulating hormone; fT4, free thyroxine 4; ROS, Reactive oxygen species; ICAM, Endothelial adhesion molecule; BC, Black carbon; HAEC, Human aortic endothelial cells; HUVEC, Human umbilical vein endothelial cells; TLR2, Toll Like Receptor 2; TLR4, Toll Like Receptor 4; IL-1 β, Interleukin 1β; IL-6, Interleukin 6; MHC, Mouse pulmonary microvascular endothelial cells; TGF-β1, Transforming growth factor-β 1; Smad3, Mothers against decapentaplegic homolog 3; p-Smad3, Phospho-Smad3; ERK, Extracellular signal regulated protein kinase; p38, Family is a highly evolutionarily conserved group of mitogen-activated protein kinases; JNK, c-Jun N-terminal kinase; AT1R, Angiotensin II type 1 receptor; HIF1α, hypoxia inducible factor 1 subunit alpha; ACE, Angiotensin-Converting enzyme; ANGII, Angiotensin II; PSA DW10, diesel engine manufactured by Peugeot S.A; NO, Nitric oxide; ET-1, Endothelin 1; 8-OHdG, 8-Hydroxy-2'-deoxyguanosine; 1-HP, 1-hydroxypyrene; HMWPAHs, High-molecular-weight polycyclic aromatic hydrocarbons; HTR-8/SVneo, Immortalized first trimester human trophoblast cells; hCGβ, Human chorionic gonadotropin β; TIMP1, Tissue inhibitor of metalloproteinase 1; TIMP2, Tissue inhibitor of metalloproteinase 2; G2/M arrest, Cell cycle arrest at the G2/M phase occurs when DNA is damaged; PAHs, Polycyclic Aromatic Hydrocarbons; GSH: Glutathione; LMWPAHs, Low-molecular-weight polycyclic aromatic hydrocarbons; MDA, malondialdehyde; B[a]P–DNA or BaP-DNA, DNA binding by Benzo[a]pyrene; B[a]P or BaP, Benzo[a]pyrene; JEG-3 cells, Human choriocarcinoma cell line; 3H-BP, 3H-benzo(a)pyrene (BP); BPDE-DNA, DNA binding by Benzo(a)pyrene diolepoxide; Swan71 cells, Immortalized human trophoblast cells; hCG, Human chorionic gonadotropin; SOD, Superoxide dismutase; NLRP3, NOD-, LRR- and pyrin domain-containing protein 3; IL-1β, interleukin-1beta; VEGF, Vascular Endothelial Growth Factor; n.a, not available; CI, Confidence interval. Particulate matter from urban samples was understood as a mixture of exhaust and non-exhaust emissions.