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孕期人尿中雌激素和孕激素代谢物的动态变化。

Dynamic change of estrogen and progesterone metabolites in human urine during pregnancy.

作者信息

Jin Chen, Peng Ying, Luo Xiaoyan, Zhu Qi, Lin Langqi, Yang Jinying, Wang Pan

机构信息

Shenzhen Key Laboratory of Steroid Drug Discovery and Development, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, Guangdong, China.

Longgang Maternity and Child Institute of Shantou University Medical College (Longgang District Maternity & Child Healthcare Hospital of Shenzhen City), Shenzhen, 518172, Guangdong, China.

出版信息

Sci Rep. 2025 Mar 11;15(1):8409. doi: 10.1038/s41598-025-92866-0.

DOI:10.1038/s41598-025-92866-0
PMID:40069295
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11897187/
Abstract

Endogenous estrogen and progesterone and their metabolites play a key role in regulating and maintaining the normal pregnancy process. However, the dynamic change of these estrogen and progesterone metabolites' level across the entire gestational period is not fully revealed. This study systematically measures the temporal changes of estrogen, progesterone, and their metabolites in human urine during normal pregnancy using ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We find that the levels of estrone, estradiol, estriol, 16-epiestriol, 17-epiestriol, 2-methoxyestradiol, and 4-hydroxyestrone gradually increase during pregnancy. The levels of 2-hydroxyestrone, 2-hydroxyestradiol, and 4-hydroxyestradiol rapidly decrease in the early pregnancy and then maintain at lower levels. The levels of 4-methoxyestradiol, 4-methoxyestrone and 2-methoxyestrone peak in the mid-pregnancy and then gradually decrease. The levels of pregnenolone, 17α-hydroxy pregnenolone, 17α-hydroxy progesterone, pregnanolone, epipregnanolone gradually increase during pregnancy. The levels of progesterone, 20α-hydroxy progesterone, 5α-dihydroprogesterone and 5β-dihydroprogesterone first increase in the mid pregnancy and then decrease in the late pregnancy. In sum, this study comprehensively depicts the dynamic change of estrogen, progesterone, and their metabolites in human urine during pregnancy, which lays the foundation for hormone monitoring and early diagnosis of pregnancy complications, and further mechanistic study of the roles of these metabolites in pregnancy.

摘要

内源性雌激素、孕激素及其代谢产物在调节和维持正常妊娠过程中起关键作用。然而,这些雌激素和孕激素代谢产物在整个妊娠期的水平动态变化尚未完全揭示。本研究采用超高效液相色谱-串联质谱法(UPLC-MS/MS)系统地测量了正常妊娠期间人尿中雌激素、孕激素及其代谢产物的时间变化。我们发现,雌酮、雌二醇、雌三醇、16-表雌三醇、17-表雌三醇、2-甲氧基雌二醇和4-羟基雌酮的水平在孕期逐渐升高。2-羟基雌酮、2-羟基雌二醇和4-羟基雌二醇的水平在妊娠早期迅速下降,然后维持在较低水平。4-甲氧基雌二醇、4-甲氧基雌酮和2-甲氧基雌酮的水平在妊娠中期达到峰值,然后逐渐下降。孕烯醇酮、17α-羟基孕烯醇酮、17α-羟基孕酮、孕烷醇酮、表孕烷醇酮的水平在孕期逐渐升高。孕酮、20α-羟基孕酮、5α-双氢孕酮和5β-双氢孕酮的水平在妊娠中期先升高,然后在妊娠晚期下降。总之,本研究全面描绘了妊娠期间人尿中雌激素、孕激素及其代谢产物的动态变化,为激素监测和妊娠并发症的早期诊断以及这些代谢产物在妊娠中作用的进一步机制研究奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/78e5dcd5e43b/41598_2025_92866_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/450bccc12d3e/41598_2025_92866_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/5ed763992675/41598_2025_92866_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/63802fb7ceff/41598_2025_92866_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/cca996bca413/41598_2025_92866_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/4bd7d347367d/41598_2025_92866_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/243934f17d63/41598_2025_92866_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/6470b2017263/41598_2025_92866_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/e70cb3b4227f/41598_2025_92866_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/78e5dcd5e43b/41598_2025_92866_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/450bccc12d3e/41598_2025_92866_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/5ed763992675/41598_2025_92866_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/63802fb7ceff/41598_2025_92866_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/cca996bca413/41598_2025_92866_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/4bd7d347367d/41598_2025_92866_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/243934f17d63/41598_2025_92866_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/6470b2017263/41598_2025_92866_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/e70cb3b4227f/41598_2025_92866_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5017/11897187/78e5dcd5e43b/41598_2025_92866_Fig9_HTML.jpg

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本文引用的文献

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Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.4-羟基雌酮对雌激素受体阴性人乳腺癌细胞中铁死亡的强烈保护作用:蛋白二硫键异构酶作为保护的机制靶点的证据。
Biochemistry. 2024 Apr 16;63(8):984-999. doi: 10.1021/acs.biochem.3c00261. Epub 2024 Apr 3.
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Reference data on estrogen metabolome in healthy pregnancy.健康妊娠雌激素代谢组学参考数据。
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Sex hormone signaling and regulation of immune function.
性激素信号转导与免疫功能调节。
Immunity. 2023 Nov 14;56(11):2472-2491. doi: 10.1016/j.immuni.2023.10.008.
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Role of Oxidative Stress and Inflammation in Gestational Diabetes Mellitus.氧化应激和炎症在妊娠期糖尿病中的作用。
Antioxidants (Basel). 2023 Sep 29;12(10):1812. doi: 10.3390/antiox12101812.
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Metabolic alteration of circulating steroid hormones in women with gestational diabetes mellitus and the related risk factors.妊娠期糖尿病患者循环类固醇激素代谢改变及其相关危险因素。
Front Endocrinol (Lausanne). 2023 Jun 15;14:1196935. doi: 10.3389/fendo.2023.1196935. eCollection 2023.
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The pathophysiological role of estrogens in the initial stages of pregnancy: molecular mechanisms and clinical implications for pregnancy outcome from the periconceptional period to end of the first trimester.雌激素在妊娠早期的病理生理作用:从围孕期到孕早期结束的分子机制及其对妊娠结局的临床意义。
Hum Reprod Update. 2023 Nov 2;29(6):699-720. doi: 10.1093/humupd/dmad016.
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Estrogen as a key regulator of energy homeostasis and metabolic health.雌激素作为能量平衡和代谢健康的关键调节剂。
Biomed Pharmacother. 2022 Dec;156:113808. doi: 10.1016/j.biopha.2022.113808. Epub 2022 Oct 15.
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Placental expression of estrogen-related receptor gamma is reduced in fetal growth restriction pregnancies and is mediated by hypoxia†.胎盘组织中雌激素相关受体 γ 的表达在胎儿生长受限妊娠中减少,这是由缺氧介导的。
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