Deterioration of mitochondrial biogenesis and degradation in the endometrium is a cause of subfertility in cows

Deterioration of mitochondrial biogenesis and degradation in the endometrium is a cause of subfertility in cows
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线粒体生物发生的恶化和子宫内膜的降解是奶牛生育能力低下的一个原因

DOI:
10.1002/mrd.23670
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发表时间:
2023
影响因子:
2.5
通讯作者:
Kimura Koji
Kimura Koji
中科院分区:
生物学3区
文献类型:
--
作者:
Matsuyama Shuichi;Nakamura Sho;Minabe Shiori;Sakatani Miki;Takenouchi Naoki;Sasaki Takuya;Inoue Yuki;Iwata Hisataka;Kimura Koji

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为了研究繁殖失败的可能原因,我们对生育能力较强和生育能力较差的奶牛进行了整体子宫内膜基因表达分析。独创性途径分析表明,RICTOR和SIRT3是可育奶牛高表达基因的重要上游调节因子,并被预测为正常线粒体呼吸的上游调节因子。典型通路分析表明,这些高表达的基因参与了线粒体氧化磷酸化的激活。因此,在生育不良的奶牛中,RICTOR和SIRT3的失活可能与线粒体呼吸能力下降有关。此外,大多数线粒体DNA基因和编码线粒体蛋白的核基因在不孕奶牛中的表达水平较高。低能育奶牛子宫内膜线粒体DNA拷贝数显著高于低能育奶牛,而ATP含量在低能育奶牛和低能育奶牛之间差异不显著。定量逆转录-聚合酶链式反应分析表明,PGC1a、TFAM、Mfn1、FIS1和BCL2L13在不育奶牛中的表达显著降低。此外,透射电子显微镜图像显示,未生育奶牛的子宫内膜细胞中线粒体肿胀。这些结果表明,在不育奶牛中,由于线粒体生物发生、融合、分裂和降解能力的降低,劣质线粒体在子宫内膜中积累,可能是不孕的原因之一。
To investigate possible causes of reproductive failure, we conducted global endometrial gene expression analyses in fertile and subfertile cows. Ingenuity pathway analysis showed that RICTOR and SIRT3 are significant upstream regulators for highly expressed genes in fertile cows, and are predicted to be activated upstream regulators of normal mitochondrial respiration. Canonical pathway analysis revealed that these highly expressed genes are involved in the activation of mitochondrial oxidative phosphorylation. Therefore, in subfertile cows, the inactivation of RICTOR and SIRT3 may correlate with decreased capacity of mitochondrial respiration. Furthermore, the expression levels of most mitochondrial DNA genes and nuclear genes encoding mitochondrial proteins were higher in subfertile cows. The mitochondrial DNA copy number was significantly higher in the endometrium of subfertile cows, whereas the ATP content did not differ between fertile and subfertile cows. Quantitative reverse transcription‐PCR analysis demonstrated that the expression ofPGC1a, TFAM, MFN1, FIS1, andBCL2L13were significantly lower in subfertile cows. In addition, transmission electron microscopy images showed mitochondrial swelling in the endometrial cells of the subfertile cow. These results suggest that poor‐quality mitochondria accumulate in the endometrium owing to a reduced capacity for mitochondrial biogenesis, fusion, fission, and degradation in subfertile cows, and may contribute to infertility.
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发表时间: 1980-01-01
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