Influence Of Ovarian Function By Kengshengmycin And Etoposide And Protective Effects Of Cetrorelix In Mice

Objective: To observe the influence of ovarian function and fetus by kengshengmycin and etoposide, and offer the experiment basis for choosing the chemotherapeutants in clinic. To investigate the protective effects of cetrorelix on chemotherapy-induced ovarian damage in female mice, and offer another method to protect ovarian function in clinic.Methods: Sixty BALB/c mice were divided into six groups: control group, KSM group, VP16 group, cyclophosphamide(CTX) group, cetrorelix group and CTX+cetrorelix group, which were received normal saline, KSM, VP16, CTX, cetrorelix and CTX+ cetrorelix. We killed half of the mice, both ovaries of each mice were removed to measure the amount of primordial follicles, primary follicles, secondary follicles, preantral follicles, antral follicles, the total number of follicles and morphology of ovary. The rest mice were mated with males, and bred until delivery. Pregnancy rates and fetal malformation were determined. After lactation, the rest mice were killed and both ovaries were removed to observe ibidem.Results:1. Compared with follicular numbers of each group, when mice were killed after given medicine:there was no significant difference between KSM group, VP16 group and control group. All levels follicular numbers and total follicular numbers in CTX group were significantly fewer than those in the control group (P<0.05), the primordial follicle reduced 55%. In cetrorelix group, preantral and antral follicular numbers were significantly fewer than those in the control group(2.4±1.3,1.2±1.3 versus 5.8±1.9,4.0±1.6), but the other levels follicular numbers and total follicular numbers did not decrease. Compared with CTX group, CTX+ cetrorelix groupdeveloped a significantly greater number of primordial follicles and total follicles, which increased 2.06 and 1.96 times respectively. While compared with control group, there was no significant difference between them.2. Compared with two different times (killed after given medicine and killed after lactation) in the same group: there was no significant difference in both KSM group and VP16 group. The number of antral follicles in cetrorelix group increased from 1.2±1.3 to 3.8±1.8 (P<0.05), the other levels follicular numbers and total follicular numbers has no significant difference. There was no significant difference between two different times in CTX+ cetrorelix group.3. Morphology of ovary: compared with control group, there was no significant difference in both KSM group and VP16 group. CTX group: different stage follicles significantly decreased, tissues are fibrosis and necrosis, granulosa cells were abnormal. Cetrorelix group: a number of primordial follicles appeared, preantral and antral follicles were fewer, there was no tissue fibrosis, granulosa cells were normal. CTX+ cetrorelix group: all levels follicles can be observed, but most of follicles were primordial follicles; tissue fibrosis was lightly and necrosis was rare; granulosa cells were normal.4. Pregnancy rates and average fetal number were no significant different between each group. Twenty-nine fetuses were born and we did not observe fetal malformations.Conclusions:1. KSM at 70μg/kg·d×10d dose has no effects on follicular numbers, and do not effect ovarian function in mice.2. VP16 at 25mg/kg·d×5d dose has no effects on follicular numbers, and do not effect ovarian function in mice.3.Cetrorelix has some protective effects on cyclophosphamide–induced ovarian damage in mice.