Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring.

Ambient fine particulate matter (PM2.5) exposures during pregnancy could lead to adverse birth outcomes, including neurobehavioral development defects. However, limited studies explored the effects and potential epigenetic mechanisms of maternal PM2.5 exposure on offspring spatial memory defects. This study aims to explore the effects and underlying epigenetic mechanisms of maternal concentrated ambient PM2.5 exposure in male mice offspring with spatial memory defects. Pregnant female C57BL/6 mice were exposed daily to concentrated ambient PM2.5 (CAP) or filtered air (FA) throughout gestation, with the concentration of particulates (102.99 ± 78.74 µg/m3) and (2.78 ± 1.19 µg/m3), respectively. Adult male mice offspring were subsequently assessed for spatial learning and memory ability using Morris Water Maze tests and locomotor activities in open field tests. The hippocampus of the male mice offspring was harvested to test mRNA expression and DNA methylation. Results from the probe test of Morris Water Maze showed that the mice offspring in the CAP group had shorter swimming distance travelled in the target quadrant, shorter duration in the target quadrant, and less number of entries into the target quadrant (p < 0.05), suggesting spatial memory impairments. The acquisition trials of Morris Water Maze did not show a significant difference in learning ability between the groups. The mRNA level of interleukin 6 (IL-6) in the CAP group hippocampus (10.80 ± 7.03) increased significantly compared to the FA group (1.08 ± 0.43). Interestingly, the methylation levels of the CpG sites in the IL-6 promoter region declined significantly in the CAP group, (5.66 ± 0.83)% vs. (4.79 ± 0.48)%. Prenatal exposure to concentrated ambient PM2.5 induced long-lasting spatial memory defects in male mice offspring. The underlying biological mechanism might be mediated by an inflammatory reaction which is regulated by DNA methylation.

Hydrogen ameliorates lung injury in a rat model of subacute exposure to concentrated ambient PM2.5 via Aryl hydrocarbon receptor.

BACKGROUND: Ambient fine particulate matter (PM2.5) could induce lung injury. Aryl hydrocarbon receptor (AhR) is involved in the molecular mechanisms of prooxidative and pro-inflammatory effect of PM2.5. Molecular hydrogen has antioxidant properties. The protective effect and mechanism of hydrogen on PM2.5-induced lung injury remain unclear. OBJECTIVES: This study aimed to determine whether hydrogen could alleviate lung injury in a rat model of subacute exposure to concentrated ambient PM2.5, and explore the mechanism related to AhR. METHODS: Male Wastar rats were exposed to either concentrated ambient particles (CAPs) (diameter: ≤2.5 µm, average concentration: 1328 ±â€¯730 µg/m3) or filtered air (FA) by nose-only inhalation (5 h/day, 5 days/week for 4 weeks). Hydrogen-treated rats inhaled 66.7% hydrogen from water electrolysis for 2 h after each exposure to CAPs or FA. RESULTS: CAPs inhalation induced lung injury, as demonstrated by pulmonary function decrease, histopathological damage, mucus hypersecretion [Periodic acid-Schiff (PAS) staining for mucins, immunohistochemistry and quantitative real-time PCR (RT-qPCR) for mucin 5AC (MUC5AC) expression], increased pro-inflammatory cytokines (TNF-α, IL-8 and IL-1ß) and oxidative damage indexes [malondialdehyde (MDA) and 8-isoprostane F2α (8-iso-PG)]. While, hydrogen inhalation significantly alleviated the damages mentioned above. In addition, low expression of AhR in lung tissues determined by Western Blot was found after CAPs exposure, whereas hydrogen inhibited AhR decline induced by CAPs. CONCLUSIONS: High concentrations of hydrogen could ameliorate pulmonary dysfunction, airway mucus hypersecretion, oxidation damage, and inflammation response in rats exposed to concentrated ambient PM2.5. Additionally, hydrogen alleviates lung injury induced by PM2.5 possibly through AhR-dependent mechanisms.