Adverse Effects of Prenatal Exposure to Oxidized Black Carbon Particles on the Reproductive System of Male Mice.

Ambient black carbon (BC), a main constituent of atmospheric particulate matter (PM), is a primary particle that is mainly generated by the incomplete combustion of fossil fuel and biomass burning. BC has been identified as a potential health risk via exposure. However, the adverse effects of exposure to BC on the male reproductive system remain unclear. In the present study, we explored the effects of maternal exposure to oxidized black carbon (OBC) during pregnancy on testicular development and steroid synthesis in male offspring. Pregnant mice were exposed to OBC (467 µg/kg BW) or nanopure water (as control) by intratracheal instillation from gestation day (GD) 4 to GD 16.5 (every other day). We examined the testicular histology, daily sperm production, serum testosterone, and mRNA expression of hormone synthesis process-related factors of male offspring at postnatal day (PND) 35 and PND 84. Histological examinations exhibited abnormal seminiferous tubules with degenerative changes and low cellular adhesion in testes of OBC-exposed mice at PND 35 and PND 84. Consistent with the decrease in daily sperm production, the serum testosterone level of male offspring of OBC-exposed mice also decreased significantly. Correspondingly, mRNA expression levels of hormone-synthesis-related genes (i.e., StAR, P450scc, P450c17, and 17ß-HSD) were markedly down-regulated in male offspring of PND 35 and PND 84, respectively. In brief, these results suggest that prenatal exposure has detrimental effects on mouse spermatogenesis in adult offspring.

Interactions between oxidative stress, autophagy and apoptosis in A549 cells treated with aged black carbon.

After emitted from incomplete combustion of fossil fuels and biomass, ambient black carbon (BC) was then undergone photochemical oxidization processes in the air to form aged BC particles, also called oxidized BC (OBC). This study aimed to investigate the interactions between oxidative stress, autophagy and apoptosis induced by OBC in A549 cells and to explore associated molecular mechanisms. First, OBC could stimulate oxidative stress, autophagy and apoptosis dose-dependently, as evidenced by increased intercellular reactive oxygen species (ROS) levels, up-regulated autophagosome markers (light chain 3, LC3), and elevated apoptosis rate. Inhibitors of oxidative stress (N-acetylcysteine, NAC), autophagy (bafilomycin A1, Baf) and apoptosis (Z-DEVD-FMK) were used to investigate their interactions. NAC pretreatment could significantly reduce autophagy and apoptosis. Additionally, pretreatment with Baf or Z-DEVD-FMK could also significantly suppress the other two biological effects. Furthermore, OBC up regulated the expressions of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), phosphorylated protein kinase B (Akt) and mammalian target of rapamycin (mTOR). The Akt inhibitor (MK-2206) significantly reduced both autophagy and apoptosis. Taken together, dual-direction regulation existed between each two of oxidative stress, autophagy, and apoptosis in A549 cells exposed to OBC. In addition, the autophagy process is modulated by the PI3K/Akt pathway regardless of mTOR activity.

MAP4K4 deficiency in CD4(+) T cells aggravates lung damage induced by ozone-oxidized black carbon particles.

As the main composition of combustion, black carbon (BC) is becoming more and more noticeable at home and abroad. Ozone-oxidized black carbon (oBC) was produced through aging of ozone, one of the near-surface pollutants, to black carbon. And oBC was found to be more oxidation and cell toxicity when compared with BC. Besides, as a key cell of immunity, whether CD4(+) T cell would involve in lung inflammation induced by particular matter is still unclear. This study aims to observe the effect of oBC on lung damage in mice and discuss how the functional MAP4K4 defect CD4(+) T cells (conditional knockout of MAP4K4) presents its role in this process. In our study, MAP4K4 deletion in CD4(+) T cells (MAP4K4 cKO) could increase cell number of macrophages, lymphocytes and neutrophils in bronchoalveolar lavage fluid (BALF) exposed to oBC. MAP4K4 deletion in CD4(+) T cell also affected CD4(+) T cell differentiation in mediastinal lymph nodes after oBC stimulation. The number of CD4(+) IL17(+) T cell increased obviously. The levels of IL-6 mRNA of lung in MAP4K4 cKO mice was higher than that in wild type mice after exposed to oBC, while the level of IL-6 in BALF had the same trend. Histological examination showed that MAP4K4 deletion in CD4(+) T cells affected lung inflammation induced by oBC. Results indicated that MAP4K4 cKO in CD4(+) T cells upgraded the level of inflammation in lung when exposed to oBC, which may be connected to the CD4(+) T cell differentiation and JNK, ERK and P38 pathways.