| Silica nanoparticles（SiO2-NPs） has a small particle size, a large specific surface area and active center, and to be applied in various fields, such as cosmetics, pharmaceutical, construction, and electronic. Si O2-NPs can enter into human body through breathing, skin contact and food. It can transport into human organs through blood circulation and lymph circulation, having an potential impact on human health. The development and function of ovary are strictly controlled by the hypothalamic- pituitary-gonadal axis（HPG axis）. Under the influence of external adverse factors, follicular differentiation, maturation and ovulation were affected. Women appear to be more vulnerable to adverse external factors. SiO2-NPs is used as abortion drugs in clinical practice. But the effect and its mechanism of SiO2-NPs on the female reproductive systemis still unknown.To characterize the effects of Si O2-NPs on the female ovarian toxicity and its molecular mechanism, behavior changes of zebrafish were studied. Moreover, female ovarian toxicity of SiO2-NPs were deeply studied in cells and molecules lever by methods, including cell proliferation, oxidative stress, DNA damage, realtive gene and protein expression.The main results of this study are as follows:（1） Swimming behavior changes of zebrafish were affected significantly in 600 and 1200mg/L dose groups. Swimming speed was decreased 30%-50% 6h after exposure. Changes of swimming dept lagged behind changes of swimming speed, which were decreased by more than 90% 24 h after exposure. Group behavior of zebrafish was also changed, distance and dispersion were significantly decreased（all p<0.01）.（2） 24 h half lethal concentration SiO2-NPs in zebrafish ovarian stromal cells（IC50） is 49.265mg/L. Compared with control group, SOD activity, MDA content were significantly increased（p<0.05）, and CAT activity were significantly decreased（p<0.05） in dose groups after 24 h exposure; the activity of LDH were increased, but no significant difference. SCGE results showed that tail DNA, tail length, tail length of ovarian stromal cells were increased significant（p<0.01） after exposure. Expression of reproductive hormone related genes such as Lhb and Vtg1 was increased significantly（p<0.05） in 2mg/L and 8 mg/L dose group, but expression of Lhr was decreased significantly（p<0.01）. Moreover, expression of tet2, mbd2, Brg1 and snrpb was also increased significantly（p<0.05）.（3）Under transmission electron microscope, it was observed that SiO2-NPs could distribute into ovarian tissue at 600 and 1200mg/L dose group, but pathological changes were not found obviously. Compared with control group, ovarian coefficient was significantly decreased（p<0.05） after exposure. Expression of Lhr was significantly decreased（p<0.01） in 1200 mg/L dose group, while expression of mbd2 was increased significantly（p<0.01）. Meanwhile, expression profile of LHR and MBD2 protein were similar as the genes.In conclusion, compared to injury or death of zebrafish, the swimming behavior of zebrafish（swimming speed,swimming depth, turning frequency, distance and dispersion） were changed earlier by SiO2-NPs exposure, which can realize the early warning function of SiO2-NPs. SiO2-NPs has genetic toxicity, which can enter into zebrafish ovary, induce ovarian histopathological changes and increase of oxidative stress, DNA damage, and apoptosis in zebrafish; and also can inhibit expression of hormone receptor（LHR） and MBD2 in vitro and in vivo to disrupt HPG axis balance and may cause cancer. |
PDF Full Text Request