Nonoxynol-9 induces apoptosis of endometrial explants by both caspase-dependent and -independent apoptotic pathways.
Nonoxynol-9 induces apoptosis of endometrial explants by both caspase-dependent and -independent apoptotic pathways.
复制标题
Nonoxynol-9 通过 caspase 依赖性和非依赖性凋亡途径诱导子宫内膜外植体凋亡。
DOI：
10.1095/biolreprod.104.037168
复制
发表时间：
2005
影响因子：
3.6
通讯作者：
Felix,JuanC
中科院分区：
文献类型：
--
作者：
Jain,JohnK;Li,Aimin;Nucatola,DeborahL;Minoo,Parviz;Felix,JuanC
配制成阴道凝胶的避孕杀微生物剂为妇女控制避孕和预防艾滋病毒感染提供了可能性。这些凝胶对上生殖道的影响在很大程度上是未知的。本研究的目的是确定壬苯醇醚-9（N-9）是否诱导凋亡的人子宫内膜作为一个模型的子宫内膜外植体。通过凝胶电泳检测DNA片段化，并通过免疫组织化学使用M30 CytoDEATH和抗裂解半胱天冬酶-3（CASP 3）抗体检测半胱天冬酶活性，测定细胞凋亡。测量广谱半胱天冬酶抑制剂和CASP 3特异性抑制剂防止N-9诱导的细胞死亡的能力。采用实时荧光定量聚合酶链反应（PCR）分析肿瘤相关基因如BCL 2、BAX、Fas受体（FAS）和Fas配体（FASLG）的表达。这项研究表明，N-9诱导的DNA片段和caspase活性在子宫内膜外植体的剂量和时间依赖性的方式。Caspase抑制剂不能完全阻止N-9诱导的DNA片段化。实时荧光定量PCR分析显示，N-9处理后，FAS和FASLG显著增加。总之，这些结果表明，在子宫内膜外植体中由N-9触发的凋亡是通过FAS和FASLG介导的上游，随后是CASP 3激活，导致最终的细胞死亡。除半胱天冬酶外，其他因子也参与了N-9诱导的细胞凋亡。
Contraceptive microbicides formulated as vaginal gels offer the possibility of women-controlled contraception and prevention of HIV infection. The effects of these gels on the upper reproductive tract are largely unknown. The purpose of this study was to determine whether nonoxynol-9 (N-9) induces apoptosis in human endometrium using endometrial explant as a model. Apoptosis was determined by gel electrophoresis for the detection of DNA fragmentation and by immunohistochemistry using the M30 CytoDEATH and anti-cleaved caspase-3 (CASP3) antibodies for the detection of caspase activity. The ability of the broad-spectrum caspase inhibitor and CASP3-specific inhibitor to prevent N-9-induced cell death was measured. Expression of apoptosis-related genes such asBCL2, BAX,Fas receptor (FAS), and Fas ligand (FASLG) was quantified using real-time polymerase chain reaction (PCR) analysis. This study demonstrated that N-9 induced DNA fragmentation and caspase activity in endometrial explants in a dose- and time-dependent manner. Caspase inhibitors did not fully prevent the N-9-induced DNA fragmentation. Real-time PCR analysis revealed thatFASandFASLGwere largely increased following N-9 treatment. Together, these results suggested that apoptosis triggered by N-9 in endometrial explants is mediated upstream viaFASandFASLG, followed by CASP3 activation leading to final cell death. It appears that other factors besides caspases are also involved in the N-9-induced apoptosis.