Liang Qiande, Xu Wangyanjun, Hong Qian, Xiao Chengrong, Yang Liang, Ma Zengchun, Wang Yuguang, Tan Hongling, Tang Xianglin, Gao Yue
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, P. R. China.
Eur J Mass Spectrom (Chichester). 2015;21(6):801-21. doi: 10.1255/ejms.1395.
Metabolite differences between sexes have rarely been observed in a global manner, but it has recently been made possible by the advancement in metabolomics techniques. In this study, untargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry and an in-house software platform were used for a rapid comparison of sex differences in urinary metabolites in humans and in urinary and serum metabolites in Sprague Dawley (SD) rats. In addition, the species differences of urinary metabolites between humans and SD rats were also observed. Principle component analysis showed that all the observed metabolite sex differences were more distinct in SD rats than in humans, indicating that the sex differences of human urinary metabolites is small compared with that of SD rats. In SD rats, the observed metabolite sex differences were more distinct in urine than in serum, indicating the importance of urine analysis for metabolomics studies. The species differences in the urinary metabolites of humans and SD rats were much more distinct than any of the observed sex differences. Many sex- and species-related markers were discovered and putatively identified. In both humans and SD rats, steroid metabolites appeared to constitute a major sex difference in urinary metabolites. This provides new proof of the special importance of steroid metabolites in sex differences from an untargeted metabolomics investigation, which is rare for sex differences. Contrary patterns involving adrenocortical activity appeared to exist between rodents and humans, which agrees with previous reports. In the serum metabolites of SD rats, sex differences in ascorbic acid or its isomer and pantothenic acid or its isomer, but not in steroid metabolites, were prominent. Human-specific α-N- phenylacetyl-l-glutamine and androsterone glucuronide were among the putative identities of the markers discriminating humans and SD rats. This study demonstrated the feasibility of an in-house software platform and provides metabolite-related information on sex and species differences.
性别间的代谢物差异很少以全局方式被观察到，但代谢组学技术的进步使其近来成为可能。在本研究中，非靶向超高效液相色谱与飞行时间质谱联用以及一个内部软件平台被用于快速比较人类尿液代谢物以及斯普拉格-道利（SD）大鼠尿液和血清代谢物中的性别差异。此外，还观察到了人类与SD大鼠尿液代谢物的物种差异。主成分分析表明，所有观察到的代谢物性别差异在SD大鼠中比在人类中更明显，这表明与SD大鼠相比，人类尿液代谢物的性别差异较小。在SD大鼠中，观察到的代谢物性别差异在尿液中比在血清中更明显，这表明尿液分析在代谢组学研究中的重要性。人类与SD大鼠尿液代谢物的物种差异比任何观察到的性别差异都要明显得多。发现并初步鉴定了许多与性别和物种相关的标志物。在人类和SD大鼠中，类固醇代谢物似乎构成了尿液代谢物中的主要性别差异。这从未靶向代谢组学研究中为类固醇代谢物在性别差异中的特殊重要性提供了新的证据，这在性别差异研究中是罕见的。啮齿动物和人类之间似乎存在涉及肾上腺皮质活动的相反模式，这与先前的报道一致。在SD大鼠的血清代谢物中，抗坏血酸或其异构体以及泛酸或其异构体存在性别差异，但类固醇代谢物不存在性别差异，这种差异很突出。人类特异性的α-N-苯乙酰-L-谷氨酰胺和雄甾酮葡萄糖醛酸是区分人类和SD大鼠的标志物的推定身份之一。本研究证明了内部软件平台的可行性，并提供了与性别和物种差异相关的代谢物信息。
