Effects Of Mifepristone On The Ovarian Function Of Rats

Objective:The development of follicular and ovulation can be delayed or suppressed by mifepristone. When the treatment finishied, ovarian function will recover soon. Different doses of mifepristone were administered to rats to study the effects on the ovarian function, especially on the ovarian reserve function, to supply safety evidence for clinical medication.Method:Fourty Sprague-Dawley(SD) female rats,weight 230±20g,were divided into four groups randomly:low dose of mifepristone group,middle dose of mifepristone group,high dose of mifepristone group and blank group. Daily vaginal smears were taken and stained using Quick Pap staining to ascertain cyclicity and only the rats that showed two consecutive estrous cycles were used for the experiments. Mifepristone tablets were given through gastromy for three different groups, 1.04(mg/kg/d),2.604(mg/kg/d), 10.4(mg/kg/d) , respectively in dioestrus for four weeks. Five rats of each group were sacrificed after treatment in dioestrus,the rests were killed in the third dioestrus after treatments. The ovarians of all rats were paraffin imbedded and serially sectioned at 8μm and stained with hematoxylin and eosin stain. Histology of every ovarian were observed and the total number of primordial and primary folliculars were couted by Stereology. The estradiol lever of serum were detected by chemiluminescence. The immunohistochemical SP and gray scales scan quantity analysis for the expression of active caspase-3 protein in the granulosa cells of developing follicles of the rats sacrificed after treatment in dioestrus.Results:1. The number of developing follicles decreased while corpora atreticas increased in mifepristone groups which were sacrificed after treatment in dioestrus. A great quantity of developing follicles were observed in other groups. Considerable of primordial and primary folliculars, which located down of ovarian cortex, were observed in various groups.2. The number of primordial and primary follicles in disparate groups have no significant differences.3. After treatment, Estrogen level decreased with the accrescenced dosage of mifepristone, there were differences between blank group and high dose group. Estrogen level of mifepristone groups were recovered in the third dioestrus after treatments.4. The active caspase-3 proteins, which were detected by immunohistochemistry, were expressed in granulosa cells of developing follicles,the positive expression increased with the accrescenced dosage of mifepristone. Conclusion:1. Four weeks using of mifepristone can inhibin the growth of developing follicles and depress the surum estrogen lever with dose dependent, ovarian function will recover in the third dioestrus after treatments. Four weeks using of mifepristone can't induce atresia of primordial and primary folliculars, have no influence on the ovarian reserve of rats.2. Modulating the expression of caspase-3 protein may be one of pathway correlate with apoptosis of granular cells in ovarian induced by mifepristone, which can induce atresia of developing folliculars.