School of Public Health , Shandong University , 44 Wenhua Xi Road , Jinan , Shandong 250012 , P.R. China.
Chem Res Toxicol. 2019 Oct 21;32(10):1989-1996. doi: 10.1021/acs.chemrestox.9b00119. Epub 2019 Sep 16.
Carbon disulfide (CS) induces embryo implantation disorders. Macrophages participate in the process of pregnancy. Therefore, we want to explore the effects of CS exposure on polarization and immune function of macrophages in pregnant mice uteri. The exposure times were gestation days 3 (GD3), 4 (GD4), and 5 (GD5), and the observation end points were arranged in a time series after CS exposure. The uterine tissues were collected to detect the expression levels of macrophages cytokines (IL-6, IL-12, TGF-β1, and Vegf-a) and downstream regulatory cytokines of Th1-type (IL-2 and IFN-γ) and Th2-type (IL-10 and IL-4) by flow cytometry, ELISA, and q-PCR. The results showed that, compared with the controls, the ratios of M1/M2 macrophages in the endometrium significantly increased by 96%, 110%, and 177% at the GD4, GD6, and GD7 observation end points after GD3 exposure and increased about 3.88-fold and 2.37-fold at the GD6 and GD7 observation end points after GD4 exposure, respectively. In contrast, the ratio of M1 and M2 macrophages significantly reduced by 53% at the GD5 observation end point after GD3 exposure. Meanwhile, the expression levels of IL-6 were significantly increased about 2.00-fold for mRNA and 1.60-fold for protein at GD4 observation end points after GD3 exposure, and the mRNA levels of IL-12 increased about 3.61-fold at the GD6 observation end points after GD4 exposure. The mRNA levels of TGF-β1 were significantly decreased by 41%, 25%, and 20% at the GD7 observation end points after exposure at GD3, GD4, and GD5, and the expression levels of Vegf-a mRNA and protein were decreased. Furthermore, the ratio of IL-2/IL4, IL-2/IL-10, IFN-γ/IL-4, and IFN-γ/IL-10 in the uterine tissue was significantly increased at the exposure groups. These findings suggest that the imbalanced polarization of macrophages is the key regulator in the progress of CS-induced embryo loss.
二硫化碳（CS）可导致胚胎着床障碍。巨噬细胞参与妊娠过程。因此，我们希望探讨 CS 暴露对孕鼠子宫巨噬细胞极化和免疫功能的影响。暴露时间分别为妊娠第 3 天（GD3）、第 4 天（GD4）和第 5 天（GD5），暴露后以时间序列方式设置观察终点。收集子宫组织，采用流式细胞术、ELISA 和 q-PCR 检测巨噬细胞细胞因子（IL-6、IL-12、TGF-β1 和 Vegf-a）和 Th1 型（IL-2 和 IFN-γ）及 Th2 型（IL-10 和 IL-4）下游调节细胞因子的表达水平。结果显示，与对照组相比，GD3 暴露后 GD4、GD6 和 GD7 观察终点时，子宫内膜中 M1/M2 巨噬细胞比值分别显著增加 96%、110%和 177%，GD4 暴露后 GD6 和 GD7 观察终点时分别增加约 3.88 倍和 2.37 倍；而 GD3 暴露后 GD5 观察终点时，M1 和 M2 巨噬细胞比值则显著降低 53%。同时，GD4 观察终点时，IL-6mRNA 和蛋白表达水平分别显著增加 2.00 倍和 1.60 倍，GD4 暴露后 GD6 观察终点时，IL-12mRNA 表达水平增加 3.61 倍。GD3、GD4 和 GD5 暴露后 GD7 观察终点时，TGF-β1mRNA 表达水平分别显著降低 41%、25%和 20%，Vegf-amRNA 和蛋白表达水平降低。此外，子宫组织中 IL-2/IL4、IL-2/IL-10、IFN-γ/IL-4 和 IFN-γ/IL-10 的比值在暴露组中显著增加。这些结果提示，巨噬细胞极化失衡是 CS 诱导胚胎丢失进展的关键调控因素。
