Establishment of Effective Mouse Model of Premature Ovarian Failure Considering Treatment Duration of Anticancer Drugs and Natural Recovery Time.
Establishment of Effective Mouse Model of Premature Ovarian Failure Considering Treatment Duration of Anticancer Drugs and Natural Recovery Time.
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DOI：
10.6118/jmm.2018.24.3.196
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发表时间：
2018-12-01
期刊：
影响因子：
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通讯作者：
Lee, Kyu Sup
中科院分区：
文献类型：
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作者：
Lee, Eun Hee;Han, Si Eun;Lee, Kyu Sup
目的：本研究的目的是建立最有效的卵巢早衰（POF）小鼠模型，环磷酰胺（CTX），布磺胺（Bu），顺铂考虑抗癌药物的治疗时间和自然恢复时间。方法：对6 ~ 8周龄C57BL/6雌性小鼠腹腔注射CTX (120 mg/kg)/Bu (12 mg/kg) 1 ~ 4周或顺铂（2 mg/kg） 3 ~ 14天诱导POF。对照组在相同时间段内注射等量生理盐水。每周测定体重，末次注射抗癌药后测定卵巢和子宫重量。用妊娠母马血清促性腺激素和人绒毛膜促性腺激素诱导pof诱导小鼠超排卵，并与雄性交配，以评估其卵巢功能。18小时后取出受精卵，培养4天。最后，在最后一次注射抗癌药物后，对小鼠进行一段时间的不处理，评估卵巢功能自然恢复的时间。结果：CTX/Bu注射2周后，卵巢、子宫重量及卵巢功能明显下降。顺铂治疗10天，卵巢和子宫重量明显下降，卵巢功能明显下降。当CTX/Bu组诱导POF至少2周，顺铂组诱导POF至少10天时，卵巢功能分别在2周和1周内没有自然恢复。结论：CTX/Bu治疗至少2周，顺铂治疗至少10天，才能建立最有效的原发性卵巢功能不全小鼠模型。
OBJECTIVES: This study was aimed to establish the most effective premature ovarian failure (POF) mouse model using Cyclophosphamide (CTX), busulfan (Bu), and cisplatin considering treatment duration of anticancer drugs and natural recovery time.METHODS: POF was induced by intraperitoneally injecting CTX (120 mg/kg)/Bu (12 mg/kg) for 1 to 4 weeks or cisplatin (2 mg/kg) for 3 to 14 days to C57BL/6 female mice aged 6 to 8 weeks. Controls were injected with equal volume of saline for the same periods. Body weight was measured every week, and ovarian and uterine weights were measured after the last injection of anticancer drug. To assess ovarian function, POF-induced mice were superovulated with pregnant mare serum gonadotropin and human chorionic gonadotropin, and then mated with male. After 18 hours, zygotes were retrieved and cultured for 4 days. Finally, the mice were left untreated for a period of times after the final injection of anticancer drug, and the time for natural recovery of ovarian function was evaluated.RESULTS: After 2 weeks of CTX/Bu injection, ovarian and uterine weights, and ovarian function were decreased sharply. Cisplatin treatment for 10 days resulted in a significant decrease in ovarian and uterine weight, and ovarian function. When POF was induced for at least 2 weeks for CTX/Bu and for at least 10 days for cisplatin, ovarian function did not recover naturally for 2 weeks and 1 week, respectively.CONCLUSIONS: These results suggest that CTX/Bu should be treated for at least 2 weeks and cisplatin for at least 10 days to establish the most effective primary ovarian insufficiency mouse model.