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尿前列腺素代谢产物作为人类分娩的生物标志物:对未来预测指标的见解

Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors.

作者信息

Wood Eilidh M, Hornaday Kylie K, Newton Matthew, Wang Melinda, Wood Stephen L, Slater Donna M

机构信息

Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Department of Obstetrics and Gynaecology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

出版信息

PLoS One. 2025 Jul 14;20(7):e0315484. doi: 10.1371/journal.pone.0315484. eCollection 2025.

DOI:10.1371/journal.pone.0315484
PMID:40658667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12258607/
Abstract

Prostaglandins and other related molecules in the eicosanoid family have long been implicated in the process of both term and preterm labour. Although, exactly which eicosanoids are involved and whether they have utility as biomarkers for labour, remains to be shown. The objective of this study was to determine whether urinary prostaglandins and related molecules a) change with labour and/or cervical changes, at term and preterm, and/or b) are associated with timing of delivery in individuals with threatened preterm labour. Pregnant individuals were recruited into the following groups: n = 32 term non-labour, n = 49 term labour, n = 15 preterm non-labour controls, n = 43 threatened preterm labour with preterm delivery, and n = 44 threatened preterm labour with term delivery. Metabolites of prostaglandins PGE2, PGF2α, PGD2, and PGI2 as well as 8-isoprostane were measured by ELISA. In addition, in a small (n = 24) subset of samples, 147 eicosanoids were measured using a mass-spectrometry based targeted lipidomics panel. At term labour prostaglandin PGF2α and PGE2 and PGF2α metabolites were increased compared to term non-labour. There were no changes in any prostaglandin metabolites prior to labour onset. Prostaglandin I2 metabolite was lower in individuals with threatened preterm labour who delivered preterm compared to those who went on to deliver at term. In our discovery cohort, we identified 20 additional eicosanoids as highly expressed in maternal urine, include members of the prostaglandin, hydroxyeicosatetraenoic acid (HETE), epoxyeicosatrienoic acid (EET), dihydroxy-octadecenoic acid (DiHOME), dihydroxy-eicosatrienoic acid (diHETrE), isoprostane, and nitro fatty acid eicosanoid families. In conclusion, we did not identify any prostaglandins that would have utility as predictors for term or preterm labour, however, we have identified diverse eicosanoids that have not been previously explored in the context of pregnancy and labour, highlighting novel areas for biomarker research.

摘要

类花生酸家族中的前列腺素及其他相关分子长期以来一直被认为与足月分娩和早产过程有关。然而,究竟哪些类花生酸参与其中,以及它们是否可作为分娩的生物标志物,仍有待证实。本研究的目的是确定尿前列腺素及相关分子:a)在足月和早产时是否会随着分娩和/或宫颈变化而改变,和/或b)与先兆早产个体的分娩时间是否相关。将孕妇分为以下几组:n = 32例足月未分娩者,n = 49例足月分娩者,n = 15例早产未分娩对照者,n = 43例先兆早产并早产者,以及n = 44例先兆早产并足月分娩者。通过酶联免疫吸附测定法(ELISA)测量前列腺素PGE2、PGF2α、PGD2和PGI2以及8-异前列腺素的代谢物。此外,在一个小样本(n = 24)子集中,使用基于质谱的靶向脂质组学检测板测量了147种类花生酸。与足月未分娩相比,足月分娩时前列腺素PGF2α、PGE2和PGF2α代谢物增加。分娩开始前,任何前列腺素代谢物均无变化。与足月分娩者相比,先兆早产并早产者的前列腺素I2代谢物较低。在我们的发现队列中,我们确定了另外20种类花生酸在母体尿液中高表达,包括前列腺素、羟基二十碳四烯酸(HETE)、环氧二十碳三烯酸(EET)、二羟基十八碳烯酸(DiHOME)、二羟基二十碳三烯酸(diHETrE)、异前列腺素和硝基脂肪酸类花生酸家族的成员。总之,我们未发现任何可作为足月或早产预测指标的前列腺素,然而,我们确定了多种以前在妊娠和分娩背景下未被探索过的类花生酸,突出了生物标志物研究的新领域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/88313d450738/pone.0315484.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/b36d2f983f7e/pone.0315484.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/c45c658ade39/pone.0315484.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/ff0b21a6c791/pone.0315484.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/88313d450738/pone.0315484.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/b36d2f983f7e/pone.0315484.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/c45c658ade39/pone.0315484.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/ff0b21a6c791/pone.0315484.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c006/12258607/88313d450738/pone.0315484.g004.jpg

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本文引用的文献

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Vaginal misoprostol versus vaginal dinoprostone for cervical ripening and induction of labour: An individual participant data meta-analysis of randomised controlled trials.阴道用米索前列醇与阴道用地诺前列酮用于宫颈成熟和引产:一项随机对照试验的个体参与者数据荟萃分析。
BJOG. 2024 Aug;131(9):1167-1180. doi: 10.1111/1471-0528.17794. Epub 2024 Feb 29.
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The hormonal control of parturition.分娩的激素控制。
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Signaling Pathways Regulating Human Cervical Ripening in Preterm and Term Delivery.
调控早产和足月分娩时人宫颈成熟的信号通路。
Cells. 2022 Nov 21;11(22):3690. doi: 10.3390/cells11223690.
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Functional and pathological role of 15-Lipoxygenase and its metabolites in pregnancy and pregnancy-associated complications.15-脂氧合酶及其代谢产物在妊娠及妊娠相关并发症中的功能和病理作用。
Prostaglandins Other Lipid Mediat. 2022 Aug;161:106648. doi: 10.1016/j.prostaglandins.2022.106648. Epub 2022 May 13.
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Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? A systematic review.是否存在一种母体血液生物标志物可以在分娩发作前预测自发性早产?系统评价。
PLoS One. 2022 Apr 4;17(4):e0265853. doi: 10.1371/journal.pone.0265853. eCollection 2022.
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Prostaglandins in biofluids in pregnancy and labour: A systematic review.生物流体中的前列腺素在妊娠和分娩中的作用:系统评价。
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Up-regulation of cytosolic prostaglandin E synthase in fetal-membrane and amniotic prostaglandin E2 accumulation in labor.细胞质前列腺素 E 合酶在胎儿膜和分娩时羊水中前列腺素 E2 积累中的上调。
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Mid-gestation serum lipidomic profile associations with spontaneous preterm birth are influenced by body mass index.中孕期血清脂质组学特征与自发性早产的相关性受体重指数影响。
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