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将线粒体动力学与生育能力联系起来:通过凤凰素调节 GnRH 受体和线粒体动力学蛋白 DRP-1 和 Mfn-2 在卵巢中的表达来提高生育能力。

Linking mitochondrial dynamics and fertility: promoting fertility by phoenixin through modulation of ovarian expression of GnRH receptor and mitochondrial dynamics proteins DRP-1 and Mfn-2.

机构信息

Department of Medical Physiology, Faculty of Medicine, Tanta University, Tanta, Egypt.

Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Pflugers Arch. 2022 Oct;474(10):1107-1119. doi: 10.1007/s00424-022-02739-y. Epub 2022 Aug 16.

DOI:10.1007/s00424-022-02739-y
PMID:35972578
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9492611/
Abstract

Obesity is linked to reproductive disorders. Novel neuropeptide phoenixin demonstrated many therapeutic actions. In this study, we aim to evaluate phoenixin's potential effect in obesity-induced infertility through modulating mitochondrial dynamics. Ninety adult female rats were divided to 4 groups: (I), fed with normal pellet diet; (II), given phoenixin; (III), fed with high-fat diet. Rats that developed obesity and infertility were divided to 2 groups: (III-A), received no further treatment; (III-B), given phoenixin. Our results showed that phoenixin treatment in obese infertile rats significantly decreased serum levels of insulin and testosterone and ovarian levels of dynamin-related protein1(Drp1),reactive oxygen species ROS, TNF-α, MDA, and caspase-3. Phoenixin treatment also significantly increased serum estrogen progesterone, LH, and FSH together with ovarian levels of GnRH receptor (GnRHR), mitofusin2(Mfn2), mitochondrial transmembrane potential (ΔΨm), and electron transport chain (ETC) complex-I significantly when compared with obese group. Ovarian histopathological changes were similarly improved by phoenixin. Our data demonstrate phoenixin's role in improving obesity-induced infertility.

摘要

肥胖与生殖障碍有关。新型神经肽凤凰素表现出许多治疗作用。在这项研究中,我们旨在通过调节线粒体动力学来评估凤凰素在肥胖引起的不孕中的潜在作用。将 90 只成年雌性大鼠分为 4 组:(I),喂以正常颗粒饮食;(II),给予凤凰素;(III),给予高脂肪饮食。肥胖和不孕的大鼠分为 2 组:(III-A),不进行进一步治疗;(III-B),给予凤凰素。我们的结果表明,肥胖不孕大鼠给予凤凰素治疗后,血清胰岛素和睾酮水平以及卵巢中动力相关蛋白 1(Drp1)、活性氧(ROS)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)和半胱天冬酶-3(caspase-3)水平显著降低。与肥胖组相比,凤凰素治疗还显著增加了血清雌激素、孕激素、LH 和 FSH 水平,以及卵巢中的促性腺激素释放激素受体(GnRHR)、线粒体融合蛋白 2(Mfn2)、线粒体跨膜电位(ΔΨm)和电子传递链(ETC)复合物-I 水平。凤凰素还改善了卵巢的组织病理学变化。我们的数据表明凤凰素在改善肥胖引起的不孕中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/483c66ce0af4/424_2022_2739_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/ae1cb5027853/424_2022_2739_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/483c66ce0af4/424_2022_2739_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/d86a08311cee/424_2022_2739_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/c60acf805b6e/424_2022_2739_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/e2ec90524efb/424_2022_2739_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/f31ef8024823/424_2022_2739_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/6ee4a2dcfde5/424_2022_2739_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/0f3e50740e21/424_2022_2739_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/ae1cb5027853/424_2022_2739_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3565/9492611/483c66ce0af4/424_2022_2739_Fig8_HTML.jpg

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Drug Des Devel Ther. 2020 Sep 22;14:3865-3874. doi: 10.2147/DDDT.S258857. eCollection 2020.
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Obesity, Insulin Resistance, and Hyperandrogenism Mediate the Link between Poor Diet Quality and Ovarian Dysmorphology in Reproductive-Aged Women.肥胖、胰岛素抵抗和高雄激素血症介导了不良饮食质量与生殖期妇女卵巢形态异常之间的关联。
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Phoenixin 14 inhibits ischemia/reperfusion-induced cytotoxicity in microglia.
The role of mitofusin 2 in regulating endothelial cell senescence: Implications for vascular aging.
线粒体融合蛋白2在调节内皮细胞衰老中的作用:对血管衰老的影响。
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High-fat diet-negative impact on female fertility: from mechanisms to protective actions of antioxidant matrices.高脂肪饮食对女性生育能力的负面影响:从作用机制到抗氧化基质的保护作用
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Current state of phoenixin-the implications of the pleiotropic peptide in stress and its potential as a therapeutic target.凤凰肽的现状——这种多效性肽在应激中的意义及其作为治疗靶点的潜力
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凤凰素 14 抑制小胶质细胞缺血/再灌注诱导的细胞毒性。
Arch Biochem Biophys. 2020 Aug 15;689:108411. doi: 10.1016/j.abb.2020.108411. Epub 2020 May 23.
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