The Study Of A Novel Copper-containing Composite IUD On The Antifertility Effectiveness And Expression Levels Of Factors Associated With IUD Side Effects In The Endometrium Of Rat

Objectives:The study was conducted to investigate the antifertility effectiveness of cupric chloride/silicon dioxide/poly(vinyl alcohol)(CuCl2/SiO2/PVA) nanocomposite IUD and its ability of restore fertility after removal in rats.Methods:One hundred and sixty female Sprague-Dawley (SD) rats aged10-12weeks, were randomly divided into six groups:sham-operated control group (SO group, n=20), bulk copper group (Cu group, n=30), SiO2/PVA group (n=30), CuCl2/Si02/PVA groups I (copper ion released at5-10ug/220mm2per day, n=30) and Ⅱ (copper ion released at10-20ug/220mm2per day, n=30) and normal control group(NC group, n=20). After30days of insertion, twenty of the rats in each group, ten from SO group and ten from NC group, were mated with male rats of proven fertility, and the antifertility rates (ATs) were observed at Day14of pregnancy. After the IUDs were removed, the remaining rats in each group were mated again to prove their fertility.Results:ATs in the Cu group and the CuCl2/SiO2/PVA groups I and II were100%. And each of these rates was significantly higher than those in the other groups (p<0.05). There were no differences in fertility restoration rates after the IUD was removed among the Cu group and the CuCl2/SiO2/PVA group Ⅰ (p>0.05).Conclusion:The new design of the CuCl2/SiO2/PVA nanocomposite IUD shows as high and reversible contraceptive efficacy as bulk copper IUD. Objectives:To evaluate the safety of a novel copper-containing composite IUD by testing the cupric ion concentrations in the serum and local uterine fluid in rats.Methods:Sixty female Sprague-Dawley (SD) rats aged10-12weeks, were randomly divided into six groups:sham-operated control group (SO group, n=10), bulk copper group (Cu group, n=10), SiO2/PVA group (n=10), CuCl2/Si02/PVA groups I (n=10) and Ⅱ (n=10) and normal control group (NC group, n=10). At different time points after60days since implantation, cupric ion concentrations were measured in the serum and local uterine fluid in each group by flame atomic absorption, respectively.Results:No significant change in time dependence was found for the serum cupric ion concentrations in each group (p>0.05), while the local uterine fluid cupric ion concentrations in other groups were significantly lower than those in the Cu group (p<0.05).During the first week after implantation, cupric ion concentrations in each group, except for SiO2/PVA group, rise significantly. Cupric ion concentrations in uterine fluid in CuCl2/SiO2PVA groups is at peak on Day5, while cupric ion concentrations in bulk copper group continue to rise after Day5. Cupric ion concentrations in uterine fluid in CuCl2/SiO2/PVA group is significantly lower than those of bulk copper group (p<0.05).Conclusion:The novel copper-containing composite used in intrauterine contraceptive devices (CuCl2/SiO2/PVA composite IUD) has neither a burst release of cupric ions nor accumulation of cupric ions in the initial days of application. Objectives:To evaluate the safety of a novel copper-containing composite IUD by exploring the endometrial morphological changes after being inserted with IUD.Methods:Fifty female Sprague-Dawley (SD) rats aged10-12weeks, were randomly divided into five groups:bulk copper group (Cu group, n=10), SiO2/PVA group (n=10), CuCl2/SiO2/PVA groups Ⅰ (n=10) and Ⅱ (n=10) and normal control group (NC group, n=10). After the insertion of IUD for30and60days, endometrial tissues and important organs were obtained from different groups. The morphological characteristics of the samples were observed and evaluated by Hematoxylin-Eosin (HE) staining technique and transmission electron microscope, respectively.Results:Morphologic changes of the important organs and the endometria of the rats in all IUD groups were observed. Compared with the Cu group, the microscopic characteristics of the CuCl2/SiO2/PVA group were milder; and no other important tissues and important organs injury were observed on Day30and Day60in all IUD groups; The impact of the Cu group on ultrastructure of rat endometrium showed irregular pattern of microvilli of epithelial cells, big vacuole and swollen mitochondria cristae in cytoplasm, increased microfilaments and broadened cell-cell junction in Day30and even severer in Day60. The ultrastructure changes of CuCl2/SiO2/PVA group I were more slight and had no significant difference on Day30and Day60.Conclusion:Compared with conventional bulk copper IUD, the novel Copper-containing IUD has less effect on the morphological changes of endometrium and induces minor endometrium damage, which may relieve the side-effects of copper bearing IUD insertion. Objectives:To detect the expression levels of factors associated with IUD side effects (bleeding and pain) in the endometrium of rat, and to explore the effects of novel copper-containing composite IUD on rat uterine internal environment and the mechanism of reducing side effects caused by Cu-IUD.Methods:Forty sexually mature female Sprague-Dawley (SD) rats were randomly divided into four groups:bulk copper group (Cu group, n=10), CuCl2/SiO2/PVA groups Ⅰ (n=10) and Ⅱ (n=10) and normal control group (NC group, n=10). The expression levels of factors associated with IUD side effects (SP, SPR, MMP9, TIMP-1, EGF and Flkl) in the endometrium of rats were detected by quantitative real-time polymerase chain reaction, Western blotting and immunohistochemistry technique in each group after insertion of IUD in Day60.Results:SP and SPR were mainly expressed around the endometrial blood vessels and in the cytoplasm of mesenchymal cells. MMP9and TIMP-1were widely expressed on the endometrial epithelioglandular cells, endometrial stroma and vascular endothelial cells. VEGF and Flkl were expressed on the endometrial epithelioglandular cells and endometrial stroma. The mRNAs and proteins expressions of all factors except TIMP-1in Cul2/SiO2/PVA group were significiantly lower than those in Cu group (P<0.05), especially in CuCl2/Si02/PVA group Ⅰ (P<0.01).Conclusion:Compared with conventional bulk copper material, the novel Copper-containing IUD has lower expression levels of factors associated with bleeding and pain. It may be one mechanism of this material on relieving the side-effect of Cu-IUD.