Mechanisms by which female stress and particularly glucocorticoids impair oocyte competence are largely unclear. Although one study demonstrated that glucocorticoids triggered apoptosis in ovarian cells and oocytes by activating the FasL/Fas system, other studies suggested that they might induce apoptosis through activating other signaling pathways as well. In this study, both in vivo and in vitro experiments were conducted to test the hypothesis that glucocorticoids might trigger apoptosis in oocytes and ovarian cells through activating the TNF-α system. The results showed that cortisol injection of female mice (1.) impaired oocyte developmental potential and mitochondrial membrane potential with increased oxidative stress; (2.) induced apoptosis in mural granulosa cells (MGCs) with increased oxidative stress in the ovary; and (3.) activated the TNF-α system in both ovaries and oocytes. Culture with corticosterone induced apoptosis and activated the TNF-α system in MGCs. Knockdown or knockout of TNF-α significantly ameliorated the pro-apoptotic effects of glucocorticoids on oocytes and MGCs. However, culture with corticosterone downregulated TNF-α expression significantly in oviductal epithelial cells. Together, the results demonstrated that glucocorticoids impaired oocyte competence and triggered apoptosis in ovarian cells through activating the TNF-α system and that the effect of glucocorticoids on TNF-α expression might vary between cell types.

中文翻译：

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糖皮质激素通过激活 TNF-α 系统损害卵母细胞能力并触发卵巢细胞凋亡

女性压力，特别是糖皮质激素损害卵母细胞能力的机制尚不清楚。尽管一项研究表明糖皮质激素通过激活 FasL/Fas 系统触发卵巢细胞和卵母细胞的凋亡，但其他研究表明它们也可能通过激活其他信号通路诱导细胞凋亡。本研究通过体内外实验验证了糖皮质激素可能通过激活 TNF-α 系统触发卵母细胞和卵巢细胞凋亡的假设。结果表明，雌性小鼠(1.)注射皮质醇会损害卵母细胞发育电位和线粒体膜电位，氧化应激增加；(2.) 在卵巢氧化应激增加的情况下诱导壁颗粒细胞 (MGCs) 凋亡；和（3。) 激活卵巢和卵母细胞中的 TNF-α 系统。皮质酮培养诱导细胞凋亡并激活 MGC 中的 TNF-α 系统。敲除或敲除 TNF-α 可显着改善糖皮质激素对卵母细胞和 MGC 的促凋亡作用。然而，皮质酮培养显着下调了输卵管上皮细胞中 TNF-α 的表达。总之，结果表明糖皮质激素通过激活 TNF-α 系统损害卵母细胞能力并引发卵巢细胞凋亡，并且糖皮质激素对 TNF-α 表达的影响可能因细胞类型而异。敲除或敲除 TNF-α 可显着改善糖皮质激素对卵母细胞和 MGC 的促凋亡作用。然而，皮质酮培养显着下调了输卵管上皮细胞中 TNF-α 的表达。总之，结果表明糖皮质激素通过激活 TNF-α 系统损害卵母细胞能力并引发卵巢细胞凋亡，并且糖皮质激素对 TNF-α 表达的影响可能因细胞类型而异。敲除或敲除 TNF-α 可显着改善糖皮质激素对卵母细胞和 MGC 的促凋亡作用。然而，皮质酮培养显着下调了输卵管上皮细胞中 TNF-α 的表达。总之，结果表明糖皮质激素通过激活 TNF-α 系统损害卵母细胞能力并引发卵巢细胞凋亡，并且糖皮质激素对 TNF-α 表达的影响可能因细胞类型而异。