Clinical Medicine Division, Korea Institute of Oriental Medicine, 1672 Yuseongdae-ro, Yuseong-gu, Daejeon, 34054, Republic of Korea.
BMC Pharmacol Toxicol. 2021 Jan 7;22(1):3. doi: 10.1186/s40360-020-00468-5.
Most patients with cancer undergo multiple administrations of anticancer drugs during treatment, resulting in chronic impairment of their reproductive health. As improved treatment options increase cancer survival, it has become increasingly important to address fertility issues in cancer survivors. In this study, we examined the pathophysiological effects of multiple exposures to cyclophosphamide (Cy) on the ovaries of mice and their underlying molecular mechanism.
Female C57BL/6 mice were intraperitoneally injected with 100 mg/kg Cy six times over 2 weeks; 4 weeks later, the mice were sacrificed and their ovaries, sera, and oocytes were collected for histological observation, measurement of anti-Müllerian hormone levels, and assessment of oocyte quantity and quality in response to hormonal stimulation. Gene expression changes in Cy-treated ovaries were examined by microarray and bioinformatics analyses.
After repeated Cy exposure, the anti-Müllerian hormone level was decreased, and follicle loss and impairments in the quality of oocyte were irreversible. The expression levels of genes involved in folliculogenesis, oogenesis, and zona pellucida glycoprotein transcription displayed sustained alterations in Cy-exposed ovaries even after 4 weeks.
The adverse effects of Cy on ovarian function and oocytes remained even after chemotherapy was complete. Therefore, strategies to prevent ovarian damage or restore ovarian function after treatment are required to safeguard the fertility of young cancer survivors.
大多数癌症患者在治疗过程中会多次接受抗癌药物治疗，导致其生殖健康受到慢性损害。随着治疗选择的改善提高了癌症患者的生存率，解决癌症幸存者的生育问题变得越来越重要。在这项研究中，我们研究了多次接触环磷酰胺（Cy）对小鼠卵巢的病理生理影响及其潜在的分子机制。
将雌性 C57BL/6 小鼠腹腔内注射 100mg/kg Cy 六次，共 2 周；4 周后，处死小鼠并收集其卵巢、血清和卵母细胞，进行组织学观察、抗苗勒管激素水平的测量以及对激素刺激的卵母细胞数量和质量的评估。通过微阵列和生物信息学分析检测 Cy 处理的卵巢中的基因表达变化。
反复接触 Cy 后，抗苗勒管激素水平下降，卵泡丢失和卵母细胞质量受损是不可逆转的。参与卵泡发生、卵子发生和透明带糖蛋白转录的基因的表达水平在 Cy 暴露的卵巢中持续改变，即使在 4 周后也是如此。
即使化疗完成后，Cy 对卵巢功能和卵母细胞的不良影响仍然存在。因此，需要在治疗后采取策略来预防卵巢损伤或恢复卵巢功能，以保护年轻癌症幸存者的生育能力。
