LAUSR

Carbon disulfide (CS2) can cause embryo implantation disorders. Macrophages play an important role in the process of pregnancy in uterine tissues. Therefore, we want to explore the effects of CS2 exposure on polarization and immune function of macrophages in pregnant implanted uterine. The exposure times were design on gestation day 3 (GD3), 4 (GD4), and 5 (GD5), and the observation endpoints were arranged in time series after exposure to CS2. The uterine tissues were collected and the expression levels of macrophages cytokines (IL-6, IL-12, TGF-β1 and Vegf-a) and Th1-type (IL-2 and IFN-γ) and Th2-type (IL-10 and IL-4) cytokines, the downstream regulatory factors of macrophage in order to further illustrate that macrophage polarization and function change after exposure, were detected by using of the flow cytometry, ELISA, and q-PCR. The results showed that the ratios of M1 and M2 macrophages significantly increased by 96%, 110%, and 177% at the GD4, GD6, and GD7 observation endpoints after exposure at GD3, and about 3.88-fold and 2.77-fold in the endometrium at the GD6 and GD7 observation endpoints after exposure at GD4, respectively. In contrast, the ratio of M1 and M2 macrophages was significantly reduced by 53% in the GD5 observation endpoint after exposure at GD3, compared with the controls. Meanwhile, the expression levels for the immune factor secreted by the macrophages were significantly increased about 2.00-fold for IL-6 mRNA and increased by 60% for IL-6 protein at GD4 observation endpoints after GD3 exposure, and increased about 3.61-fold for IL-12 mRNA at the GD6 observation endpoints after GD4 exposure, and significantly decreased by 41%, 25%, and 20% for TGF-β1 mRNA in the GD7 observation endpoints after exposure at GD3, GD4, and GD5, compared with their corresponding control. While the expression levels of Vegf-a mRNA and the protein were significantly decreased compared with the controls. Furthermore, the ratio of IL-2 and IL-4, IL-2 and IL-10, IFN-γ and IL-4, and IFN-γ and IL-10 in the uterine tissue were significantly increased at the exposure groups, compared with their controls. These findings suggest that the unbalanced polarization macrophages was the key regulator in the embryo loss induced by CS2 exposure.