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卵巢储备功能下降进程中线粒体自噬与铁死亡的机制研究

The Mechanistic Study of Mitochondrial Autophagy and Ferroptosis in the Progression of Decreased Ovarian Reserve.

作者信息

Ma Qianwen, Wu Lifei, Wu Jianfei, Ni Binfei, Wang Jiajia, Song Shiyan

机构信息

TCM Department, Hangzhou Ninth People's Hospital, Number 98, Yilong Road, Yipeng Street, Qiantang District, Hangzhou, 311225, Zhejiang, China.

Sports Department, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.

出版信息

Reprod Sci. 2025 Apr;32(4):1202-1212. doi: 10.1007/s43032-025-01811-z. Epub 2025 Feb 13.

DOI:10.1007/s43032-025-01811-z
PMID:39948331
Abstract

OBJECTIVE

To investigate the mechanism in the progression of decreased ovarian reserve (DOR).

METHODS

Three-month-old female SD rats were employed and randomly divided into the model group and the normal group. The model group was intraperitoneally injected with 4-vinylcyclohexene diepoxide (VCD). Thereafter, blood sample from the abdominal aorta was taken, and rats were sacrificed, and ovarian tissues were obtained by laparotomy.

RESULTS

HE staining results revealed that the model group exhibited significantly reduced ovarian volume, increased follicular atresia, and decreased quantities of growing follicles and corpus luteum, thereby indicating degraded reserve function of ovarian. TEM images revealed that prominent autophagic vacuoles could be observed in the model group, accompanied by the mitochondria shrinkage and generation of the autophagosome. The expression of Pink1, Parkin, BNIP3L and LC3II genes in ovaries of the model group was significantly higher than those of the normal group (P < 0.05). In addition, the protein expression of Pink1, Parkin, BNIP3L and LC3II in ovaries of the model group were higher than those of the normal group (P < 0.05). The expression of Fe and GSH in oocytes of the model group was higher than those of the normal group (P < 0.05). The expression of FTH1 and GPX4 in oocytes of the model group was significantly higher than those of the normal group (P < 0.05).

CONCLUSIONS

Mitochondrial autophagy and ferroptosis may participate in the progression of decreased ovarian reserve (DOR).

摘要

目的

探讨卵巢储备功能下降(DOR)进展的机制。

方法

选用3月龄雌性SD大鼠,随机分为模型组和正常组。模型组腹腔注射4-乙烯基环己烯二环氧化物(VCD)。此后,采集腹主动脉血样,处死大鼠,通过剖腹术获取卵巢组织。

结果

苏木精-伊红(HE)染色结果显示,模型组卵巢体积显著减小,卵泡闭锁增加,生长卵泡和黄体数量减少,从而表明卵巢储备功能退化。透射电镜(TEM)图像显示,模型组可观察到明显的自噬泡,伴有线粒体收缩和自噬体形成。模型组卵巢中Pink1、Parkin、BNIP3L和LC3II基因的表达显著高于正常组(P < 0.05)。此外,模型组卵巢中Pink1、Parkin、BNIP3L和LC3II的蛋白表达高于正常组(P < 0.05)。模型组卵母细胞中Fe和谷胱甘肽(GSH)的表达高于正常组(P < 0.05)。模型组卵母细胞中FTH1和谷胱甘肽过氧化物酶4(GPX4)的表达显著高于正常组(P < 0.05)。

结论

线粒体自噬和铁死亡可能参与卵巢储备功能下降(DOR)的进展。

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Unraveling the Clinical Relevance of Ferroptosis-Related Genes in Human Ovarian Aging.解析铁死亡相关基因在人类卵巢衰老中的临床意义。
Reprod Sci. 2023 Dec;30(12):3529-3536. doi: 10.1007/s43032-023-01310-z. Epub 2023 Jul 27.
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NEDD4L facilitates granulosa cell ferroptosis by promoting GPX4 ubiquitination and degradation.NEDD4L通过促进GPX4泛素化和降解来促进颗粒细胞铁死亡。
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BNC1 deficiency-triggered ferroptosis through the NF2-YAP pathway induces primary ovarian insufficiency.
BNC1 缺乏通过 NF2-YAP 通路诱导铁死亡导致原发性卵巢功能不全。
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