Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model
Endometrium and endometriosis tissue mitochondrial energy metabolism in a nonhuman primate model
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DOI：
10.1186/s12958-019-0513-8
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发表时间：
2019-08-24
影响因子：
4.4
通讯作者：
Caudell, David L.
中科院分区：
文献类型：
--
作者：
Atkins, Hannah M.;Bharadwaj, Manish S.;Caudell, David L.
背景子宫内膜异位症是指子宫内膜生长到子宫外的一种疾病。在其他慢性炎症性疾病中，线粒体功能障碍被怀疑在疾病发病机制中起作用。然而，关于子宫内膜异位症线粒体功能或其对组织代谢的影响知之甚少。本研究的目的是分析非人灵长类动物（NHP）子宫内膜和子宫内膜异位症组织的线粒体功能，并确定这些组织的代谢特征，可能有助于疾病。方法使用线粒体呼吸计量分析来测量子宫内膜异位症组织和子宫内膜中的线粒体功能，以确定与临床健康NHP的对照子宫内膜相比，子宫内膜和子宫内膜异位症组织中是否存在氧化磷酸化的变化。应用靶向代谢组学和多维统计分析技术对能量和氨基酸生物合成途径中的关键代谢物进行定量。结果线粒体呼吸测定显示，在所有能量状态下，患有子宫内膜异位症的NHP的子宫内膜复合物II介导的耗氧率（OCR）均降低（基础，p = 0.01;状态3，p = 0.02;状态3u，p = 0.04;与正常子宫内膜相比，子宫内膜异位症组织具有降低的状态3、复合物I介导的OCR（p = 0.02）和呼吸控制率（p = 0.01）。对组织进行的靶向代谢组学显示，与正常子宫内膜样本相比，子宫内膜异位症组织中的肉毒碱（p = 0.001）、磷酸肌酸（p = 0.01）、NADH（p = 0.0001）、FAD（p = 0.001）、色氨酸（p = 0.0009）和苹果酸（p = 0.005）减少。与正常子宫内膜相比，患有子宫内膜异位症的NHP的子宫内膜中FAD（p = 0.004）、色氨酸（p = 0.0004）和苹果酸（p = 0.03）显著降低。在子宫内膜异位症和子宫内膜异位症动物的子宫内膜样品中鉴定的重要代谢物是氨基酸生物合成或能量代谢途径的一部分。结论子宫内膜和子宫内膜异位症组织中线粒体能量产生和代谢减少。线粒体能量产生减少可能是由于氧化应激诱导的线粒体DNA或膜损伤，细胞代谢的转变或能量底物减少;然而，确切的原因仍然未知。需要进一步的研究来确定线粒体能量产生和代谢减少对子宫内膜异位症和子宫内膜的影响。
Background Endometriosis is the growth of uterine lining (endometrium) outside of the uterus. In other chronic inflammatory diseases, mitochondrial dysfunction is suspected of playing a role in disease pathogenesis. However, little is known about endometriosis mitochondrial function or its effects on tissue metabolism. The objectives of this study were to analyze mitochondrial function in nonhuman primate (NHP) endometrium and endometriosis tissue and to identify the metabolic features of these tissues that may contribute to disease. Methods Mitochondrial function in endometriosis tissue and endometrium was measured using mitochondrial respirometry analysis to determine if changes in oxidative phosphorylation exist in endometrium and endometriosis tissue compared to control endometrium from clinically healthy NHPs. Targeted metabolomics and multidimensional statistical analysis were applied to quantify key metabolites in energy and amino acid biosynthesis pathways. Results Mitochondrial respirometry assays showed endometrium from NHPs with endometriosis had reduced complex II-mediated oxygen consumption rates (OCR) across all energy states (basal, p = 0.01; state 3, p = 0.02; state 3u, p = 0.04; state 4o, p = 0.008) and endometriosis tissue had reduced state 3, complex I-mediated OCR (p = 0.02) and respiratory control rates (p = 0.01) compared to normal endometrium. Targeted metabolomics performed on tissue revealed carnitine (p = 0.001), creatine phosphate (p = 0.01), NADH (p = 0.0001), FAD (p = 0.001), tryptophan (p = 0.0009), and malic acid (p = 0.005) were decreased in endometriosis tissue compared to normal endometrium samples. FAD (p = 0.004), tryptophan (p = 0.0004) and malic acid (p = 0.03) were significantly decreased in endometrium from NHPs with endometriosis compared to normal endometrium. Significant metabolites identified in endometriosis and endometrium samples from animals with endometriosis were part of amino acid biosynthesis or energy metabolism pathways. Conclusions Here, endometrial mitochondrial energy production and metabolism were decreased in endometrium and endometriosis tissue. Decreased mitochondrial energy production may be due to oxidative stress-induced damage to mitochondrial DNA or membranes, a shift in cell metabolism, or decreased energy substrate; however, the exact cause remains unknown. Additional research is needed to determine the implications of reduced mitochondrial energy production and metabolism on endometriosis and endometrium.