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动情前期注射线粒体融合促进剂 M1 会破坏小鼠的孕激素分泌和动情周期。

The injections of mitochondrial fusion promoter M1 during proestrus disrupt the progesterone secretion and the estrous cycle in the mouse.

机构信息

Graduate Institute of Molecular and Comparative Pathobiology, School of Veterinary Medicine, National Taiwan University, Rm. 104-1, No.1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.

School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan.

出版信息

Sci Rep. 2023 Feb 10;13(1):2392. doi: 10.1038/s41598-023-29608-7.

Abstract

After ovulation, the mitochondrial enzyme CYP11A1 cleavage the cholesterol into pregnenolone for progesterone synthesis, suggesting that mitochondrial dynamics play a vital role in the female reproductive system. The changes in the mitochondria dynamics throughout the ovarian cycle have been reported in literature, but the correlation to its role in the ovarian cycle remains unclear. In this study, mitochondrial fusion promotor, M1, was used to study the impact of mitochondria dynamics in the female reproductive system. Our results showed that M1 treatment in mice can lead to the disruptions of estrous cycles in vagina smears. The decrease in serum LH was recorded in the animal. And the inhibitions of progesterone secretion and ovulations were observed in ovarian culture. Although no significant changes in mitochondrial networks were observed in the ovaries, significant up-regulation of mitochondrial respiratory complexes was revealed in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the molecules of extracellular matrix, remodeling enzymes, and adhesion signalings were decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive systems.

摘要

排卵后,线粒体酶 CYP11A1 将胆固醇切割为孕烯醇酮以合成孕激素,这表明线粒体动力学在女性生殖系统中起着至关重要的作用。文献中已经报道了整个卵巢周期中线粒体动力学的变化,但与它在卵巢周期中的作用的相关性尚不清楚。在这项研究中,使用线粒体融合促进剂 M1 来研究线粒体动力学对女性生殖系统的影响。我们的结果表明,M1 处理可导致小鼠阴道涂片的动情周期紊乱。动物血清 LH 减少,卵巢培养观察到孕激素分泌和排卵抑制。尽管卵巢中未观察到线粒体网络的显著变化,但通过转录组分析显示 M1 处理后线粒体呼吸复合物的显著上调。与 M1 中上调的雌激素和类固醇生物合成相反,细胞外基质、重塑酶和黏附信号分子的分子减少。总之,我们的研究通过线粒体为调节卵巢周期提供了新的靶点。然而,仍需要更多的研究来提供线粒体与女性生殖系统之间的功能联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/605f/9918500/51acbcc9c369/41598_2023_29608_Fig1_HTML.jpg

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