The Study Of Hippocampus Injuries And Infertility After Nitrite Exposure

The hippocampus located in the temporal lobe is an important part of central nervous system, and plays an important role in the process of learning, memory and other physical processes. People can intake nitrite in daily life easily as its role of food additive. What’s more, nitrite as small molecular substances can affect the fetus through the placental barrier. Based on the important physiological functions of hippocampus, we studied if prenatal nitrite exposure could make hippocampus injure. In the processes of building model, we discussed the infertility effect of nitrite by experimental means.Objective: To investigate the effects on hippocampus injuries and the mouse infertility after nitrite exposure.Methods: ① Established the models of prenatal nitrite exposure with control groups( physiological saline), low dose nitrite exposure groups(60 mg/kg) and high dose nitrite exposure groups(120 mg/kg). Then, the pups of different groups at P0, P7, P14 and P30 were gathered for immunohistochemistry, comet assay and Western blotting analysis to detect the hippocampus injuries. ② Established the models of nitrite exposure with control group, low dose nitrite exposure group and high dose nitrite exposure group. The pregnant rates had been calculated among control group and nitrite exposure group. In the meantime, collecting the ovary of control group and exposure group. Pathological alterations were observed with HE staining. Furthermore, the cell apoptosis were analyzed by using TUNEL staining and Western blotting.Results: ① The hippocampus injuries of mouse pup after prenatal nitrite exposure : In both nitrite exposure groups and control groups, the number of proliferative neuron in dentate gyrus gradually decreased with the growing age; At P0, P7, P14 and P30, after prenatal nitrite exposure, BrdU positive cells decreased with dose dependency(P<0.05, n=96); In order to identify if the inhibtion is selective, we observed BrdU positive cells in subventricular zone(SVZ) at P0 mouse. The results showed: After nitrite exposure, BrdU positive cells in SVZ also decreased with dose dependency(P<0.05); The inflammatory injury and apoptosis cells in hilus increased with dose dependency after nitrite exposure(P<0.05); The comet assay showed: The tail of hippocampus cells in nitrite exposure groups were longer than that in control groups with dose dependency(P<0.01); The hippocampus expression of Caspase 8 and NF-κB protein in nitrite exposure groups were much higher than that in control groups(P<0.05). ② Nitrite exposure caused mice infertility with dose dependency(P<0.05,n=66), and the cell apoptosis in granulosa cells fllicles increased as well(P<0.01, n=20).Conclusions: ① Prenatal nitrite exposure can induce various hippocampus injuries, such as neuroproliferative inhibition, oxidative stress and neuroapoptosis; ② Nitrite exposure could lead to mice infertility. The increase of granulosa cells’ apoptosis probably was the cause of infertility.