妊娠期孕妇尿液中的外源性雌激素水平及其与代谢相关的改变
Level of Exoestrogens in Urine of Pregnant Women During Pregnancy and Related Metabolic Changes
-
摘要: 外源性雌激素是具有雌激素活性的外源性化学物质，通过模拟或抑制内源性雌激素从而干扰生物体的正常内分泌活动。处于妊娠期的孕妇摄入过量外源性雌激素不仅会对自身产生危害，还会对其胎儿产生不利影响，并且外源性雌激素摄入程度与孕妇代谢过程变化之间具有关联性。本文通过液相色谱-三重四极杆质谱联用技术测定孕妇尿液样本中的8种外源性雌激素含量，并根据样本中的外源性雌激素含量将尿液样本分为外源性雌激素水平不同的3组，在3组间有6种外源性雌激素含量具有显著性差异，其中黄豆苷原、染料木黄酮和肠内酯已被美国环境保护局列入内分泌干扰素审查程序清单中。然后，利用液相色谱-高分辨质谱联用技术分析孕妇尿液样本中的代谢组。通过多维统计分析比较外源性雌激素水平不同的孕妇尿液样本代谢组，同时筛选差异代谢物。根据差异代谢物进行生物信息分析可知，孕妇摄入不同程度外源性雌激素引起的代谢过程变化主要有氨基酸代谢、脂肪酸生物合成、柠檬酸循环和氮代谢过程等。此外，3组样本中表达差异和诊断价值较大的共同差异代谢物有甜菜碱和龙胆酸，它们和体内对抗氧化应激相关。差异代谢物反映了外源性雌激素摄入程度对孕妇代谢过程的影响，可作为生物标志物，并为外源性雌激素作用机制研究提供参考。Abstract: Exoestrogens are exogenous chemical substances with estrogenic activity, which can affect normal physiological functions by interfering with the endocrine system of humans or other animals. Intake of exoestrogens by pregnant women during pregnancy will not only cause harm to themselves, but also adversely affect their fetuses. Interestingly, there is a possible correlation between the intake level of exoestrogens and changes in the metabolic process of pregnant women. In this paper, first, the content of exoestrogens in urine samples of pregnant women was determined by liquid chromatography-triple quadrupole mass spectrometry, and the samples were classified into three groups, according to the content of exoestrogens, as “high, middle and low”. Among the three groups, the levels of daidzein, genistein, glycitein, enterodiol, enterolactone, and 3-(4-hydroxyphenyl) chroman-7-ol had a significant difference, where three of them, daidzein, genistein and enterolactone, had already been included in the list of Endocrine Disruptor Screening Program by U.S. Environmental Protection Agency. Second, metabolomes of the three groups of urine samples were analyzed by liquid chromatography-high resolution mass spectrometry, then, they were compared by multidimensional statistical analysis, and the differential metabolites were screened. There were 11 up-regulated and 6 down-regulated metabolites screened in the “high” group compared to the “middle” one, and 40 up-regulated and 40 down-regulated metabolites screened in the “middle” one compared to the “low” group. At the same time, comparison of the “high” group vs the “low” one showed 27 up-regulated and 21 down-regulated metabolites. Furthermore, bioinformatics analysis of differential metabolites showed that the metabolic process changes related to the intake level of exoestrogens mainly included amino acid metabolism, fatty acid biosynthesis, citric acid cycle and nitrogen metabolism. In addition, the common differential metabolites with a greater expression difference and diagnostic value were betaine and gentisic acid, which were related to anti-oxidative stress in vivo. Betaine is an important methyl donor in the methyl transfer reaction in vivo and can improve sulfur-containing amino acid metabolism against oxidative stress. On the other hand, gentianic acid is a polyhydroxy acid and its two phenolic hydroxyl groups are in the para position to each other, so it can play a role of antioxidant and free radical scavenger under different types of physical and chemical stimuli. In conclusion, by exploring the relationship between the intake level of exoestrogens and the changes in the metabolic process of pregnant women, this paper provides a reference for further understanding the toxicity mechanism of exoestrogens, as well as a guidance to a reasonable diet and good living habits for pregnant women.
-
-
林涵, 蒋学武. 外源性雌激素与男性生殖系统发育异常[J]. 中国男科学杂志, 2004, 18(4): 65-68 Xu Z X, Liu J, Wu X H, et al. Nonmonotonic responses to low doses of xenoestrogens: A review[J]. Environmental Research, 2017, 155: 199-207 Singleton D W, Khan S A. Xenoestrogen exposure and mechanisms of endocrine disruption[J]. Frontiers in Bioscience: A Journal and Virtual Library, 2003, 8: s110-s118 Wang L H, Chen L R, Chen K H. In vitro and vivo identification, metabolism and action of xenoestrogens: An overview[J]. International Journal of Molecular Sciences, 2021, 22(8): 4013 Hoover R N, Hyer M, Pfeiffer R M, et al. Adverse health outcomes in women exposed in utero to diethylstilbestrol[J]. The New England Journal of Medicine, 2011, 365(14): 1304-1314 Signorile P G, Spugnini E P, Mita L, et al. Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring[J]. General and Comparative Endocrinology, 2010, 168(3): 318-325 Missmer S A, Hankinson S E, Spiegelman D, et al. In utero exposures and the incidence of endometriosis[J]. Fertility and Sterility, 2004, 82(6): 1501-1508 Cai L Y, Izumi S, Suzuki T, et al. Dioxins in ascites and serum of women with endometriosis: A pilot study[J]. Human Reproduction, 2011, 26(1): 117-126 Li M L, Zhou S, Wu Y L, et al. Prenatal exposure to propylparaben at human-relevant doses accelerates ovarian aging in adult mice[J]. Environmental Pollution, 2021, 285: 117254 Toppari J, Larsen J C, Christiansen P, et al. Male reproductive health and environmental xenoestrogens[J]. Environmental Health Perspectives, 1996, 104(Suppl 4): 741-803 Tonini C, Segatto M, Bertoli S, et al. Prenatal exposure to BPA: The effects on hepatic lipid metabolism in male and female rat fetuses[J]. Nutrients, 2021, 13(6): 1970 Zhou B, Yang P, Deng Y L, et al. Prenatal exposure to bisphenol A and its analogues (bisphenol F and S) and ultrasound parameters of fetal growth[J]. Chemosphere, 2020, 246: 125805 Yang P, Lin B G, Zhou B, et al. Sex-specific associations of prenatal exposure to bisphenol A and its alternatives with fetal growth parameters and gestational age[J]. Environment International, 2021, 146: 106305 Minatoya M, Kishi R. A review of recent studies on bisphenol A and phthalate exposures and child neurodevelopment[J]. International Journal of Environmental Research and Public Health, 2021, 18(7): 3585 Zhao G F, He F, Wu C L, et al. Betaine in inflammation: Mechanistic aspects and applications[J]. Frontiers in Immunology, 2018, 9: 1070 Abedi F, Razavi B M, Hosseinzadeh H. A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology, toxicology, and some pharmaceutical aspects[J]. Phytotherapy Research, 2020, 34(4): 729-741 袁圣武, 黄超, 季晓亚, 等. 环境污染物导致氧化应激的关键信号通路及其检测方法[J]. 生态毒理学报, 2017, 12(1): 25-37 Yuan S W, Huang C, Ji X Y, et al. Main signaling pathways and detection methods of oxidative stress caused by environmental pollutants[J]. Asian Journal of Ecotoxicology, 2017, 12(1): 25-37(in Chinese)
Zhu Y, Zhang Y K, Li Y B, et al. Integrative proteomics and metabolomics approach to elucidate metabolic dysfunction induced by silica nanoparticles in hepatocytes[J]. Journal of Hazardous Materials, 2022, 434: 128820 Bordin D L, Lirussi L, Nilsen H. Cellular response to endogenous DNA damage: DNA base modifications in gene expression regulation[J]. DNA Repair, 2021, 99: 103051 Kanwar M K, Xie D L, Yang C, et al. Melatonin promotes metabolism of bisphenol A by enhancing glutathione-dependent detoxification in Solanum lycopersicum L.[J]. Journal of Hazardous Materials, 2020, 388: 121727 Wang H O, Zhao P Q, Huang Q S, et al. Bisphenol-A induces neurodegeneration through disturbance of intracellular calcium homeostasis in human embryonic stem cells-derived cortical neurons[J]. Chemosphere, 2019, 229: 618-630 Le J H, Lei X C, Ren Y P, et al. Exogenous oestradiol benzoate induces male mice azoospermia through modulation of oxidative stress and testicular metabolic cooperation[J]. Molecular Medicine Reports, 2019, 19(6): 4955-4963 Gómez-Roig M D, Pascal R, Cahuana M J, et al. Environmental exposure during pregnancy: Influence on prenatal development and early life: A comprehensive review[J]. Fetal Diagnosis and Therapy, 2021, 48(4): 245-257 Prins J R, Schoots M H, Wessels J I, et al. The influence of the dietary exposome on oxidative stress in pregnancy complications[J]. Molecular Aspects of Medicine, 2022, 87: 101098 Deng Q Y, Yin N L, Chen Y, et al. Downregulated N-acetylglucosaminyltransferase Ⅲ is involved in attenuating trophoblast migration and invasion under hypoxia–reoxygenation condition[J]. The Journal of Maternal-Fetal & Neonatal Medicine, 2019, 32(14): 2369-2375 Tang C L, Liang J, Qian J F, et al. Opposing role of JNK-p38 kinase and ERK1/2 in hydrogen peroxide-induced oxidative damage of human trophoblast-like JEG-3 cells[J]. International Journal of Clinical and Experimental Pathology, 2014, 7(3): 959-968 Curtis S, Jones C J P, Garrod A, et al. Identification of autophagic vacuoles and regulators of autophagy in villous trophoblast from normal term pregnancies and in fetal growth restriction[J]. The Journal of Maternal-Fetal & Neonatal Medicine, 2013, 26(4): 339-346 Jones M L, Mark P J, Waddell B J. Maternal dietary omega-3 fatty acids and placental function[J]. Reproduction, 2014, 147(5): R143-R152 Karamali M, Dastyar F, Badakhsh M H, et al. The effects of selenium supplementation on gene expression related to insulin and lipid metabolism, and pregnancy outcomes in patients with gestational diabetes mellitus: A randomized, double-blind, placebo-controlled trial[J]. Biological Trace Element Research, 2020, 195(1): 1-8 Wu M F, Wu Y, Xu K Z, et al. Protective effects of 1, 25 dihydroxyvitamin D3 against high-glucose-induced damage in human umbilical vein endothelial cells involve activation of Nrf2 antioxidant signaling[J]. Journal of Vascular Research, 2021, 58(4): 267-276 -
点击查看大图
计量
- 文章访问数: 1661
- HTML全文浏览数: 1661
- PDF下载数: 116
- 施引文献: 0
下载:
