背景:化疗相关卵巢损伤(CAOD)是绝经前妇女抗癌治疗最可怕的短期和长期副作用之一。积累的详细数据表明,不同的化疗方案可导致卵巢激素水平紊乱,减少或失去生育能力,更年期提前的风险增加。以前的研究往往集中在化疗药物对卵巢卵泡的直接影响,如直接DNA损伤介导的凋亡性死亡和原始卵泡倦怠。新的证据表明化疗期间卵巢微环境失衡。卵巢微环境提供营养支持和运输刺激卵泡生长和发育的信号,排卵,黄体的形成.卵巢微环境与卵泡之间的紧密相互作用可以决定卵巢功能。因此,设计新颖而精确的策略来操纵卵巢微环境可能是化疗期间保护卵巢功能的新策略。
目的:这篇综述详细介绍了化疗过程中卵巢微环境的变化,并强调了开发化疗过程中通过靶向卵巢微环境保护卵巢功能的新疗法的重要性。
方法:通过检索截至2024年4月的PubMed对文献进行了全面回顾。搜索词包括\'卵巢微环境\'(卵巢细胞外基质,卵巢基质细胞,卵巢间质,卵巢血管,卵巢淋巴管,卵巢巨噬细胞,卵巢淋巴细胞,卵巢免疫细胞因子,卵巢氧化应激,卵巢活性氧,卵巢衰老细胞,卵巢衰老相关分泌表型,卵巢卵原干细胞,卵巢干细胞),与卵巢功能相关的术语(生殖健康,生育力,不孕症,繁殖力,卵巢储备,卵巢功能,更年期,卵巢储备减少,过早的卵巢功能不全/衰竭),和与化疗相关的术语(环磷酰胺,环磷酰胺,甲基氯,苯丁酸氮芥,白消安,melphalan,丙卡巴嗪,顺铂,阿霉素,卡铂,紫杉烷,紫杉醇,多西他赛,5-氟尿嘧啶,长春新碱,甲氨蝶呤,放线菌素,博来霉素,巯基嘌呤)。
结果:化疗期间卵巢微环境有很大变化,诱导细胞外基质沉积和基质纤维化,血管生成障碍,免疫微环境干扰,氧化应激失衡,卵巢干细胞衰竭,和细胞衰老,从而降低卵泡的数量和质量。已经采用了几种针对卵巢微环境的方法来预防和治疗CAOD,如干细胞疗法和使用自由基清除剂,senolytherapies,免疫调节剂,和促血管生成因子。
结论:卵巢功能取决于其“种子”(卵泡)和“土壤”(卵巢微环境)。据报道,卵巢微环境在CAOD中起着至关重要的作用,靶向卵巢微环境可能为CAOD提供潜在的治疗方法。然而,卵巢微环境之间的关系,它的监管网络,和CAOD需要进一步研究。对这些问题的更好理解可能有助于解释CAOD的发病机理,并创造创新的策略来抵消对卵巢功能的影响。我们的目标是对CAOD的叙事回顾将激发这一重要领域的更多研究。
背景:不适用。
BACKGROUND: Chemotherapy-associated ovarian damage (CAOD) is one of the most feared short- and long-term side effects of anticancer treatment in premenopausal women. Accumulating detailed data show that different chemotherapy regimens can lead to disturbance of ovarian hormone levels, reduced or lost fertility, and an increased risk of early menopause. Previous studies have often focused on the direct effects of chemotherapeutic drugs on ovarian follicles, such as direct DNA damage-mediated apoptotic death and primordial follicle burnout. Emerging evidence has revealed an imbalance in the ovarian microenvironment during chemotherapy. The ovarian microenvironment provides nutritional support and transportation of signals that stimulate the growth and development of follicles, ovulation, and corpus luteum formation. The close interaction between the ovarian microenvironment and follicles can determine ovarian function. Therefore, designing novel and precise strategies to manipulate the ovarian microenvironment may be a new strategy to protect ovarian function during chemotherapy.
OBJECTIVE: This review details the changes that occur in the ovarian microenvironment during chemotherapy and emphasizes the importance of developing new therapeutics that protect ovarian function by targeting the ovarian microenvironment during chemotherapy.
METHODS: A comprehensive review of the literature was performed by searching PubMed up to April 2024. Search terms included \'ovarian microenvironment\' (ovarian extracellular matrix, ovarian stromal cells, ovarian interstitial, ovarian blood vessels, ovarian lymphatic vessels, ovarian macrophages, ovarian lymphocytes, ovarian immune cytokines, ovarian oxidative stress, ovarian reactive oxygen species, ovarian senescence cells, ovarian senescence-associated secretory phenotypes, ovarian oogonial stem cells, ovarian stem cells), terms related to ovarian function (reproductive health, fertility, infertility, fecundity, ovarian reserve, ovarian function, menopause, decreased ovarian reserve, premature ovarian insufficiency/failure), and terms related to chemotherapy (cyclophosphamide, lfosfamide, chlormethine, chlorambucil, busulfan, melphalan, procarbazine, cisplatin, doxorubicin, carboplatin, taxane, paclitaxel, docetaxel, 5-fluorouraci, vincristine, methotrexate, dactinomycin, bleomycin, mercaptopurine).
RESULTS: The ovarian microenvironment shows great changes during chemotherapy, inducing extracellular matrix deposition and stromal fibrosis, angiogenesis disorders, immune microenvironment disturbance, oxidative stress imbalances, ovarian stem cell exhaustion, and cell senescence, thereby lowering the quantity and quality of ovarian follicles. Several methods targeting the ovarian microenvironment have been adopted to prevent and treat CAOD, such as stem cell therapy and the use of free radical scavengers, senolytherapies, immunomodulators, and proangiogenic factors.
CONCLUSIONS: Ovarian function is determined by its \'seeds\' (follicles) and \'soil\' (ovarian microenvironment). The ovarian microenvironment has been reported to play a vital role in CAOD and targeting the ovarian microenvironment may present potential therapeutic approaches for CAOD. However, the relation between the ovarian microenvironment, its regulatory networks, and CAOD needs to be further studied. A better understanding of these issues could be helpful in explaining the pathogenesis of CAOD and creating innovative strategies for counteracting the effects exerted on ovarian function. Our aim is that this narrative review of CAOD will stimulate more research in this important field.
BACKGROUND: Not applicable.