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首页> 外文期刊>American Journal of Obstetrics and Gynecology >Impaired steroidogenesis and apoptosis of granulosa-luteal cells in primary culture induced by cis-platinum
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Impaired steroidogenesis and apoptosis of granulosa-luteal cells in primary culture induced by cis-platinum

机译:顺铂诱导原代培养的颗粒-黄体细胞类固醇生成和凋亡受损

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Objective The purpose of this study was to test the hypothesis that the cytotoxic drug cis-platinum (CP) induces premature ovarian failure by reducing the viability of human granulosa cells. Study Design We incubated cultured human granulosa-luteal cells (GLCs) with varying concentrations of CP for 48 hours. Steroidogenesis and apoptosis were assessed by progesterone and estradiol, annexin V/propidium iodide, phase contrast, and transmission electron microscopy. Results CP caused impaired production of progesterone and estradiol in a dose- and a time-dependent fashion. The estradiol production was more pronounced than progesterone for each concentration of CP that was studied. The phase contrast microscopy of CP-treated GLCs showed loss of cell number with condensed nuclei. CP-induced apoptosis was maximum at 20 μg/mL compared with a 10-μg/mL concentration (79.9% ± 4.6% vs 58.3% ± 3.9%; P <.01). The hallmark of apoptosis (ie, nuclear condensation, cell size shrinkage) was seen in CP-treated cells by transmission electron microscopy. Conclusion CP induces apoptosis of human GLCs in culture with impaired steroidogenesis, which may be one mechanism by which a CP-containing regime induces premature ovarian failure.
机译:目的本研究的目的是检验细胞毒性药物顺铂(CP)通过降低人类颗粒细胞的活力来诱导卵巢早衰的假设。研究设计我们将培养的具有不同CP浓度的人类颗粒-黄体细胞(GLC)孵育48小时。通过孕酮和雌二醇,膜联蛋白V /碘化丙啶,相差和透射电子显微镜评估类固醇生成和凋亡。结果CP以剂量和时间依赖性方式导致孕酮和雌二醇的产生受损。对于所研究的每种浓度的CP,雌二醇的产生都比孕酮更为明显。经CP处理的GLC的相差显微镜显示,细胞核数目减少,核浓缩。与10μg/ mL的浓度相比,CP诱导的细胞凋亡在20μg/ mL时最大(79.9%±4.6%对58.3%±3.9%; P <.01)。通过透射电子显微镜在CP处理的细胞中可见凋亡的标志(即,核浓缩,细胞大小缩小)。结论CP可诱导类固醇生成受损的培养物中人GLC的凋亡,这可能是含CP的方案诱发卵巢早衰的一种机制。

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