原始卵泡存活率和卵巢血管结构的变化可能在化疗期间独立调节
Wonmi So1, Rosemary Dong1, Donghee Lee2
1Olson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Endocrinology
|March 26, 2025
概括
化疗会损害卵巢毛囊和血管,导致不孕. 然而,卵巢血管系统可以从思普拉丁损伤中恢复,这表明卵泡存活和血管完整性的独立调节.
科学领域:
- 生殖生物学 生殖生物学
- 在瘤学瘤学.
- 血管生物学 血管生物学
背景情况:
- 化疗会引起性腺毒性,导致癌症幸存者的女性不孕.
- 卵巢功能对于内分泌健康和生育能力至关重要.
- 保护卵巢功能免受化疗的影响是一个重大的临床挑战.
研究的目的:
- 调查保护卵巢功能免受化疗引起的毒性的策略.
- 评估西斯丁,多克索鲁比辛和环胺对卵巢血管和原卵泡存活的作用.
- 了解化疗引起的卵巢卵泡损失和血管损伤之间的关系.
主要方法:
- 使用了成年CD-1小鼠,早期产后CD-1小鼠和卵细胞特异的Trp63条件淘汰赛 (Trp63cKO) 小鼠.
- 使用化疗药物 (cisplatin, doxorubicin, cyclophosphamide) 来评估对卵巢血管和原卵泡的影响.
- 分析了CD31/PECAM-1表达模式,并使用CK2II (检查点激酶2抑制剂) 和VEGFA165.5.
主要成果:
- 化疗剂改变了CD31/PECAM-1的表达,导致卵巢卵泡损失和卵巢血管损伤.
- 在Trp63 cKO小鼠中,血管损伤独立于原始毛囊损失发生.
- VEGFA165并没有防止毛囊损失或血管损伤.
- 卵巢血管系统在长期的ex vivo和in vivo实验中证明了西斯普拉丁诱导的损伤的恢复.
结论:
- 卵巢卵泡存活和血管完整性似乎是独立调节的过程.
- 不同的信号通路或机制可能控制原始卵泡死亡和血管损伤.
- 卵巢血管系统在化疗引起的损伤后具有恢复的能力.
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