Tumor-Derived Oxidative Stress Triggers Ovarian Follicle Loss in Breast Cancer
Tumor-Derived Oxidative Stress Triggers Ovarian Follicle Loss in Breast Cancer
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DOI：
10.1016/j.ajpath.2023.01.015
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发表时间：
2023-04-18
影响因子：
6
通讯作者：
Li，Ping
中科院分区：
文献类型：
--
作者：
Wu，Yongqi;Huang，Jieqiong;Li，Ping
乳腺癌是卵巢冷冻保存的常见适应症。然而，移植卵巢组织是否满足功能要求，以及是否需要额外的干预措施，仍不清楚。目前的研究证实了人类乳腺癌和乳腺癌细胞系衍生的荷瘤小鼠的血清激素异常，并首次显示了肿瘤诱导的原始和生长卵泡的丢失，以及由于生长或闭锁而丢失的卵泡数量。荷瘤小鼠的一项基因标记表明，类固醇生成的调控网络受到干扰，该网络通过磷脂酰肌醇3-激酶信号通路与卵母细胞和颗粒细胞的线粒体功能障碍有关。值得注意的是，在荷瘤小鼠的血清和卵巢组织中发现了增加的活性氧。此外，补充维生素C促进卵泡静止，通过使哺乳动物雷帕霉素途径的磷脂酰肌醇3-激酶- akt靶点失活来修复肿瘤诱导的卵泡损失，这表明抗氧化剂作为生育治疗的潜力，可以获得更多的健康卵泡，为卵巢冷冻保存做好准备。
Breast cancer is a common indication for ovarian cryopreservation. However, whether the grafting ovarian tissue meets functional requirements, as well as the need for additional interventions, remains unclear. The current study demonstrates abnormal serum hormones in breast cancer in humans and breast cancer cell line–derived tumor-bearing mice, and for the first time shows tumor-induced loss of primordial and growing follicles, and the number of follicles being lost to either growth or atresia. A gene signature of tumor-bearing mice demonstrates the disturbed regulatory network of steroidogenesis, which links to mitochondria dysfunction in oocytes and granulosa cells via the phosphatidylinositol 3-kinase signaling pathway. Notably, increased reactive oxygen species were identified in serum and ovarian tissues in tumor-bearing mice. Furthermore, supplementation with vitamin C promoted follicular quiescence, repairing tumor-induced follicle loss via inactivation of the phosphatidylinositol 3-kinase–Akt–mammalian target of rapamycin pathway, indicating the potential of antioxidants as a fertility therapy to achieve higher numbers of healthy follicles ready for ovarian cryopreservation.