The treatment of childhood cancer with chemotherapy drugs can result in infertility in adulthood. Newer generations of drugs are developed to replace parent drugs, with the potential benefits of less toxic side effects. For platinum alkylating-like drugs, in contrast to the parent compound cisplatin, the newer-generation drug carboplatin is reported to have reduced toxicity in some respects, despite being administered at 5-15 times higher than the cisplatin dose. Whether carboplatin is also less toxic than cisplatin to the reproductive system is unknown. Here we compare the gonadotoxic impact of cisplatin and carboplatin on female and male mouse prepubertal gonads. In vitro cultured CD1 mouse ovaries or testis fragments were exposed to either cisplatin or carboplatin for 24 h on Day 2 of culture and analysed by Day 6. A dose response for each drug was determined for the ovary (0.5, 1 & 5 μg/ml cisplatin and 1, 5 & 10 μg/ml carboplatin) and the testis (0.01, 0.05 & 0.1 μg/ml cisplatin and 0.1, 0.5 & 1 μg/ml carboplatin). For the ovary, unhealthy follicles were evident from 1 μg/ml cisplatin (73% unhealthy, P = 0.001) and 5 μg/ml carboplatin (84% unhealthy, P = 0.001), with a concomitant reduction in follicle number (P = 0.001). For the testis, the proliferating germ cell population was significantly reduced from 0.05 μg/ml cisplatin (73% reduction, P = 0.001) and 0.5 μg/ml carboplatin (75% reduction, P = 0.001), with no significant impact on the Sertoli cell population. Overall, results from this in vitro animal model study indicate that, at patient equivalent concentrations, carboplatin is no less gonadotoxic than cisplatin.

中文翻译：

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化疗药物顺铂和卡铂对青春期前小鼠性腺的比较性腺毒性。

用化疗药物治疗儿童癌症可能导致成年后不育。新一代药物的开发是为了替代母体药物，具有毒副作用较小的潜在好处。对于铂烷化类药物，与母体化合物顺铂相比，据报道新一代药物卡铂在某些方面具有降低的毒性，尽管其给药剂量比顺铂高5-15倍。卡铂对生殖系统的毒性是否也比顺铂低尚不清楚。在这里，我们比较顺铂和卡铂对雌性和雄性小鼠青春期前性腺的性腺毒性影响。体外培养的 CD1 小鼠卵巢或睾丸片段在培养第 2 天暴露于顺铂或卡铂 24 小时，并在第 6 天进行分析。确定每种药物对卵巢的剂量反应（0.5、1 和 5 μg/ml）顺铂和 1、5 和 10 μg/ml 卡铂）和睾丸（0.01、0.05 和 0.1 μg/ml 顺铂和 0.1、0.5 和 1 μg/ml 卡铂）。对于卵巢，1 μg/ml 顺铂（73% 不健康，P = 0.001）和 5 μg/ml 卡铂（84% 不健康，P = 0.001）明显出现不健康卵泡，同时卵泡数量减少（P = 0.001） ）。对于睾丸，0.05 μg/ml 顺铂（减少 73%，P = 0.001）和 0.5 μg/ml 卡铂（减少 75%，P = 0.001）相比，增殖的生殖细胞群显着减少，但对支持细胞没有显着影响细胞群。总体而言，这项体外动物模型研究的结果表明，在患者等效浓度下，卡铂的性腺毒性不低于顺铂。