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The triclosan-induced shift from aerobic to anaerobic metabolism link to increased steroidogenesis in human ovarian granulosa cells
Ecotoxicology and Environmental Safety ( IF 6.8 ) Pub Date : 2021-05-31 , DOI: 10.1016/j.ecoenv.2021.112389
Yatao Du 1 , Bin Wang 1 , Zhenzhen Cai 1 , Huihui Zhang 2 , Bo Wang 3 , Wei Liang 1 , Guangdi Zhou 1 , Fengxiu Ouyang 1 , Weiye Wang 1
Affiliation  

Triclosan (TCS) is an endocrine-disrupting chemical (EDC), which is used ubiquitously as an antimicrobial ingredient in healthcare products and causes contamination in the environment such as air, water, and biosolid-amended soil. Exposure to TCS may increase the risk of reproduction diseases and health issues. Several groups, including ours, have proved that TCS increased the biosynthesis of steroid hormones in different types of steroidogenic cells. However, the precise mechanism of toxic action of TCS on increased steroidogenesis at a molecular level remains to be elucidated. In this study, we try to address the mode of action that TCS affects energy metabolism with increased steroidogenesis. We evaluated the adverse effects of TCS on energy metabolism and steroidogenesis in human ovarian granulosa cells. The goal is to elucidate how increased steroidogenesis can occur with a shortage of adenosine triphosphate (ATP) whereas mitochondria-based energy metabolism is impaired. Our results demonstrated TCS increased estradiol and progesterone levels with upregulated steroidogenesis gene expression at concentrations ranging from 0 to 10 µM. Besides, glucose consumption, lactate level, and pyruvate kinase transcription were increased. Interestingly, the lactate level was attenuated with increased steroidogenesis, suggesting that pyruvate fate was shifted away from the formation of lactate towards steroidogenesis. Our study is gathering evidence suggesting a mode of action that TCS changes energy metabolism by predominating glucose flow towards the biosynthesis of steroid hormones. To the best of our knowledge, this is the first report that TCS presents such toxic action in disrupting hormone homeostasis.



中文翻译:

三氯生诱导的从有氧代谢到无氧代谢的转变与人卵巢颗粒细胞中类固醇生成的增加有关

三氯生 (TCS) 是一种内分泌干扰化学物质 (EDC),广泛用作保健产品中的抗菌成分,并会导致空气、水和生物固体改良土壤等环境污染。接触 TCS 可能会增加生殖疾病和健康问题的风险。包括我们在内的几个小组已经证明 TCS 增加了不同类型的类固醇生成细胞中类固醇激素的生物合成。然而,TCS 在分子水平上增加类固醇生成的毒性作用的确切机制仍有待阐明。在这项研究中,我们试图解决 TCS 通过增加类固醇生成影响能量代谢的作用方式。我们评估了 TCS 对人卵巢颗粒细胞能量代谢和类固醇生成的不利影响。目标是阐明如何在三磷酸腺苷 (ATP) 短缺而基于线粒体的能量代谢受损的情况下增加类固醇生成。我们的结果表明,TCS 增加了雌二醇和黄体酮的水平,并在 0 到 10 µM 的浓度范围内上调了类固醇生成基因的表达。此外,葡萄糖消耗、乳酸水平和丙酮酸激酶转录增加。有趣的是,乳酸水平随着类固醇生成的增加而减弱,这表明丙酮酸的命运从乳酸的形成转向类固醇生成。我们的研究正在收集证据,表明 TCS 通过主导葡萄糖流向类固醇激素的生物合成来改变能量代谢的作用模式。据我们所知,

更新日期:2021-05-31
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