Institute of Environmental Science, Shanxi University, Taiyuan, PR China.
College of Environmental & Resource Sciences, Shanxi University, Taiyuan, 030006, China.
Chemosphere. 2020 Oct;256:127133. doi: 10.1016/j.chemosphere.2020.127133. Epub 2020 May 19.
Atmospheric fine particulate matter exposure (PM) can increase the incidence and mortality of heart disease, and raise the risk of fetal congenital heart defect, which have recently drawn much attention. In this study, C57BL/6 mice were exposed to PM (approximately equivalent to 174 μg/m) by intratracheal instillation during the gestation. After birth, 10 weeks old offspring mice were divided into four groups: male exposed group (ME), female exposed group (FE), male control group (MC), female control group (FC). The pathological injury, pro-inflammatory cytokines, histone acetylation levels, and expressions of GATA-binding protein 4 (GATA4) and downstream genes were investigated. The results showed that exposure to PM in utero increased pathological damage and TNF-α and IL-6 levels in hearts of offspring mice, and effects in ME were more serious than FE. Notably, GATA4 protein levels in hearts in ME were significantly lower than that of MC, accompanied by down-regulation of histone acetyltransferase (HAT)-p300 and up-regulation of histone deacetylase-SIRT3. As GATA4 downstream genes, ratios of β-MHC gene expression to α-MHC significantly raised in ME relative to the MC. Results of chromatin immunoprecipitation (ChIP)-qPCR assay found that binding levels of acetylated histone 3 lysine 9 (H3K9ac) in GATA4 promoter region in the hearts of ME or FE were markedly decreased compared with their corresponding control groups. It suggested that maternal exposure to PM may cause cardiac injury in the offspring, heart damage of male mice was worse than female mice, in which process HAT-p300, H3K9ac, transcription factor GATA4 may play an important regulation role.
大气细颗粒物暴露（PM）可增加心脏病的发病率和死亡率，并增加胎儿先天性心脏病的风险，这一点最近引起了广泛关注。在这项研究中，通过气管内滴注将 C57BL/6 小鼠暴露于 PM（约相当于 174μg/m），在妊娠期进行。出生后，将 10 周龄的后代小鼠分为四组：雄性暴露组（ME）、雌性暴露组（FE）、雄性对照组（MC）、雌性对照组（FC）。研究了病理损伤、促炎细胞因子、组蛋白乙酰化水平以及 GATA 结合蛋白 4（GATA4）和下游基因的表达。结果表明，宫内暴露于 PM 会增加后代小鼠心脏的病理损伤和 TNF-α和 IL-6 水平，且 ME 的影响比 FE 更严重。值得注意的是，ME 心脏中的 GATA4 蛋白水平明显低于 MC，同时伴随着组蛋白乙酰转移酶（HAT）-p300 的下调和组蛋白去乙酰化酶-SIRT3 的上调。作为 GATA4 的下游基因，ME 中β-MHC 基因表达与α-MHC 的比值明显高于 MC。染色质免疫沉淀（ChIP）-qPCR 实验结果表明，与相应的对照组相比，ME 或 FE 心脏中 GATA4 启动子区域结合的乙酰化组蛋白 3 赖氨酸 9（H3K9ac）水平明显降低。这表明母体暴露于 PM 可能导致后代心脏损伤，雄性小鼠的心脏损伤比雌性小鼠更严重，在此过程中 HAT-p300、H3K9ac、转录因子 GATA4 可能发挥重要的调节作用。
