Embryo implantation dysfunction via the decreased uterine dendritic cells's non-immune function after exposed to carbon disulfide

Abstract

Objective: To study the effect of CS2 on dendritic cells (DCs) in the uterus and the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor(fms-like tyrosine kinase-1, Flt-1), and to explore the toxic mechanism of CS2-induced embryo implantation dysfunction. Methods: The Kunming mice were randomly divided into control group,gestational day 4(GD4) exposure group and GD5 exposure group. The endpoints of each group(GD5, GD6, GD7) was set up according to their respective exposure time points. The mice in the exposure group were given intraperitoneal injection of CS2 at an injection dose of 631.4 mg/kg and the control group was given olive oil. The effect of CS2 on DCs in the uterus of pregnant mice was observed by flow cytometry. The levels of VEGF and Flt-1 were measured by Real-time quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: In the GD4 and GD5 exposure groups, the number of DCs in the uterus of pregnant mice decreased at all endpoints and the GD5 endpoint in the GD4 exposure group decreased by 21%(P=0.039), when compared with the control group. In the GD4 exposure group, the levels of VEGF mRNA and protein in the uterus of the pregnant mice were 79% and 30% lower than those in the control group, respectively (P=0.03、P=0.017); the levels of Flt-1 mRNA and protein at the endpoints of GD6 and GD7 in the uterus decreased by 54%, 36%, 60% and 56%, respectively, when compared with the control group(P=0.017、P=0.012、P=0.004、P=0.007). In the GD5 exposure group, the levels of VEGF mRNA and protein in the uterus of pregnant mice at the endpoint of GD7 decreased by 62% and 36%, when compared with the control group (P=0.005、P=0.035); the levels of Flt-1 mRNA and protein in the uterus at the endpoint of GD7 decreased by 60% and 44%, respectively, when compared with the control group (P=0.004、P=0.009). Conclusion: CS2 reduced the number of DCs in the uterus of pregnant mice, and affected the non-immune function of DCs, which affected uterine angiogenesis, this may be one of the mechanisms of CS2-induced embryo implantation dysfunction.