硫酸盐不会保护卵巢储备免受西斯普拉丁诱导的性腺毒性†
Wonmi So1, Amirhossein Abazarikia1, Mary B Zelinski2,3
1Olson Center for Women's Health, Department of Obstetrics and Gynecology, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Biology of reproduction
|January 9, 2024
概括
硫酸硫酸 (STS) 能预防西斯普拉丁引起的听力损失,但不能预防卵巢储备的枯竭. 研究表明,在小鼠模型中,STS不能保护卵细胞免受西斯普拉丁诱导的DNA损伤.
科学领域:
- 在瘤学瘤学.
- 生殖生物学 生殖生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 西斯普拉丁是一种有效治疗各种瘤的化疗剂,但会引起显著的副作用,包括听力损失和卵巢储备耗尽.
- 硫酸盐 (STS) 被FDA批准用于减轻西斯胺诱导的听力损失,促使人们对其对卵巢功能保护作用进行调查.
研究的目的:
- 评估硫酸盐 (STS) 在保护卵巢储备免受西斯普拉丁诱导的性腺毒性方面的疗效.
- 调查STS保护对西斯普拉丁诱导的卵细胞损伤的时间和机制.
主要方法:
- 使用ex vivo卵巢培养和in vivo小鼠模型 (产后第7天和青少年) 来评估卵巢储备.
- 进行了免疫光测试,以检测卵细胞中的DNA损伤 (γH2AX,cPARP) 和通路激活 (pCHK2,pERK).
主要成果:
- 在活体中,STS在西斯普拉丁后给药保护了原始毛囊,但在西斯普拉丁后4-6小时给予STS时,这种效果在体内没有复制.
- 卵细胞在暴露于西斯普拉丁后,无论施用STS,都显示出DNA损伤,表明迅速敏感.
- 卵细胞死亡途径涉及pCHK2激活,与内耳细胞中的pERK途径不同.
结论:
- 虽然STS有效预防西斯普拉丁诱导的听力损失,但它不能保护小鼠模型中的卵巢储备.
- 卵细胞对西斯普拉丁诱导的性腺毒性高度敏感,不论STS治疗如何,DNA损伤都会迅速发生.
- 参与卵细胞和内耳细胞死亡的独特分子通路表明可能需要不同的保护策略.
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