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邻苯二甲酸二（2-乙基己基）酯通过破坏小鼠体内微生物-肠道-下丘脑-垂体-卵巢轴降低妊娠率。

Di (2-ethylhexyl) Phthalate decrease pregnancy rate via disrupting the microbe-gut-hypothalamic-pituitary-ovarian axis in mice.

作者信息

Xu Linjie, Yan Jun, Yin Tingting, Pan Yingzi, Chen Min, Wang Xinyan, Wu Lan, Ding Hongjuan

机构信息

Department of Obstetrics, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, Jiangsu, PR China.

出版信息

NPJ Biofilms Microbiomes. 2025 Jun 13;11(1):107. doi: 10.1038/s41522-025-00742-6.

DOI:10.1038/s41522-025-00742-6
PMID:40514374
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12166069/
Abstract

Di (2-ethylhexyl) Phthalate (DEHP), a widely used plasticizer and endocrine disruptor, poses risks to human health, particularly reproductive function. Using a mouse model, we investigated how DEHP exposure impacts the hypothalamic-pituitary-ovarian (HPO) axis through gut microbiome disruption. DEHP decreased pregnancy rates by impairing ovarian function, activating hypothalamic astrocytes, and increasing neuregulin 1 (NRG1) expression. NRG1 binding to astrocyte ErbB2 receptors elevated prostaglandin E2 (PGE2) and gonadotropin-releasing hormone (GnRH), disrupting HPO axis homeostasis. Additionally, DEHP altered gut microbiota, destabilized microbial networks, and impacted β-glucuronidase-related taxa, leading to hormone fluctuations and reduced fertility. This study highlights gut microbiome perturbations as a novel mechanism linking DEHP exposure to reproductive dysfunction. Our study provides novel insights concerning perturbations of the gut microbiome and HPO axis and their functions as a potential new mechanism by which DEHP exposes interferes with the reproductive function-related human health.

摘要

邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛使用的增塑剂和内分泌干扰物，对人类健康构成风险，尤其是对生殖功能。我们使用小鼠模型研究了DEHP暴露如何通过破坏肠道微生物群来影响下丘脑-垂体-卵巢（HPO）轴。DEHP通过损害卵巢功能、激活下丘脑星形胶质细胞和增加神经调节蛋白1（NRG1）的表达来降低怀孕率。NRG1与星形胶质细胞ErbB2受体结合会升高前列腺素E2（PGE2）和促性腺激素释放激素（GnRH），从而破坏HPO轴的稳态。此外，DEHP改变了肠道微生物群，破坏了微生物网络，并影响了与β-葡萄糖醛酸酶相关的分类群，导致激素波动和生育能力下降。这项研究强调肠道微生物群紊乱是将DEHP暴露与生殖功能障碍联系起来的一种新机制。我们的研究提供了关于肠道微生物群和HPO轴的紊乱及其作为DEHP暴露干扰生殖功能相关人类健康的潜在新机制的功能的新见解。

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Di (2-ethylhexyl) Phthalate decrease pregnancy rate via disrupting the microbe-gut-hypothalamic-pituitary-ovarian axis in mice.邻苯二甲酸二（2-乙基己基）酯通过破坏小鼠体内微生物-肠道-下丘脑-垂体-卵巢轴降低妊娠率。
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本文引用的文献

1
Gut microbial β-Glucuronidase: A key regulator of endobiotic homeostasis.肠道微生物β-葡萄糖醛酸酶：内源性稳态的关键调节因子。
Cell Host Microbe. 2024 Jun 12;32(6):783-785. doi: 10.1016/j.chom.2024.05.007.
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Gut microbiota dysbiosis promotes the development of epithelial ovarian cancer regulating Hedgehog signaling pathway.
肠道微生物失调通过调节 Hedgehog 信号通路促进上皮性卵巢癌的发展。
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Maternal microbiota and gestational diabetes: impact on infant health.母体微生物群与妊娠期糖尿病：对婴儿健康的影响。
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Reproductive toxicity of combined effects of endocrine disruptors on human reproduction.内分泌干扰物联合作用对人类生殖的生殖毒性
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Gut microbiota: a non-target victim of pesticide-induced toxicity.肠道微生物组：农药诱导毒性的非靶标受害者。
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Tebuconazole mediates cognitive impairment via the microbe-gut-brain axis (MGBA) in mice.三唑酮通过微生物-肠道-大脑轴（MGBA）介导小鼠认知障碍。
Environ Int. 2023 Mar;173:107821. doi: 10.1016/j.envint.2023.107821. Epub 2023 Feb 13.
8
Polystyrene-microplastics and DEHP co-exposure induced DNA damage, cell cycle arrest and necroptosis of ovarian granulosa cells in mice by promoting ROS production.聚苯乙烯微塑料和邻苯二甲酸二（2-乙基）己酯共同暴露通过促进 ROS 产生诱导小鼠卵巢颗粒细胞的 DNA 损伤、细胞周期停滞和坏死性凋亡。
Sci Total Environ. 2023 May 1;871:161962. doi: 10.1016/j.scitotenv.2023.161962. Epub 2023 Feb 10.
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The effect of gut microbiota dysbiosis on patients with preeclampsia.肠道微生物菌群失调对先兆子痫患者的影响。
Front Cell Infect Microbiol. 2023 Jan 4;12:1022857. doi: 10.3389/fcimb.2022.1022857. eCollection 2022.
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Prebiotic oligofructose protects against high-fat diet-induced obesity by changing the gut microbiota, intestinal mucus production, glycosylation and secretion.低聚果糖通过改变肠道微生物群、肠黏液产生、糖基化和分泌来预防高脂肪饮食诱导的肥胖。
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