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.

中文翻译：

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非人灵长类动物模型中的子宫内膜和子宫内膜异位组织线粒体能量代谢。

背景技术子宫内膜异位症是子宫外子宫内膜（子宫内膜）的生长。在其他慢性炎症性疾病中，线粒体功能障碍可能在疾病的发病机理中起作用。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。这项研究的目的是分析非人类灵长类动物（NHP）子宫内膜和子宫内膜异位症组织中的线粒体功能，并确定这些组织可能有助于疾病的代谢特征。方法使用线粒体呼吸测定法检测子宫内膜异位症组织和子宫内膜的线粒体功能，以测定子宫内膜异位症和子宫内膜异位症组织中氧化磷酸化的变化是否与临床健康NHP的对照子宫内膜相比存在。靶向代谢组学和多维统计分析用于量化能量和氨基酸生物合成途径中的关键代谢物。结果线粒体呼吸测定法显示，子宫内膜异位症NHPs的子宫内膜在所有能量状态下（基础，p = 0.01;状态3，p = 0.02;状态3u，p = 0.04;状态4o， p = 0.008），与正常子宫内膜相比，子宫内膜异位症的状态3降低，复合物I介导的OCR（p = 0.02）和呼吸控制率（p = 0.01）降低。在组织上进行的靶向代谢组学显示了肉碱（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）与正常子宫内膜样品相比，子宫内膜异位症组织中的蛋白含量降低。FAD（p = 0.004），与正常子宫内膜相比，患有子宫内膜异位的NHP子宫内膜中的色氨酸（p = 0.0004）和苹果酸（p = 0.03）明显减少。在子宫内膜异位症动物的子宫内膜异位和子宫内膜样品中鉴定出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。结论在这里，子宫内膜和子宫内膜异位症组织的子宫内膜线粒体能量产生和代谢降低。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，细胞代谢改变或能量底物减少所致。但是，确切原因仍然未知。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和子宫内膜的影响。与正常子宫内膜相比，患有子宫内膜异位的NHP子宫内膜的0004和苹果酸（p = 0.03）显着降低。在子宫内膜异位症动物的子宫内膜异位和子宫内膜样品中鉴定出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。结论在这里，子宫内膜和子宫内膜异位症组织的子宫内膜线粒体能量产生和代谢降低。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，细胞代谢改变或能量底物减少所致。但是，确切原因仍然未知。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和子宫内膜的影响。与正常子宫内膜相比，患有子宫内膜异位的NHP子宫内膜的0004和苹果酸（p = 0.03）显着降低。在子宫内膜异位症动物的子宫内膜异位和子宫内膜样品中鉴定出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。结论在这里，子宫内膜和子宫内膜异位症组织的子宫内膜线粒体能量产生和代谢降低。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，细胞代谢改变或能量底物减少所致。但是，确切原因仍然未知。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和子宫内膜的影响。03）与正常子宫内膜相比，患有子宫内膜异位的NHP的子宫内膜明显减少。在子宫内膜异位症动物的子宫内膜异位和子宫内膜样品中鉴定出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。结论在这里，子宫内膜和子宫内膜异位症组织的子宫内膜线粒体能量产生和代谢降低。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，细胞代谢改变或能量底物减少所致。但是，确切原因仍然未知。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和子宫内膜的影响。03）与正常子宫内膜相比，患有子宫内膜异位的NHP的子宫内膜明显减少。在子宫内膜异位症动物的子宫内膜异位和子宫内膜样品中鉴定出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。结论在这里，子宫内膜和子宫内膜异位症组织的子宫内膜线粒体能量产生和代谢降低。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，细胞代谢改变或能量底物减少所致。但是，确切原因仍然未知。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和子宫内膜的影响。