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

IF 7.8 1区生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

npj Biofilms and Microbiomes Pub Date : 2025-06-13 DOI:10.1038/s41522-025-00742-6

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

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引用次数: 0

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.

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

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，特别是生殖功能构成威胁。使用小鼠模型，我们研究了DEHP暴露如何通过肠道微生物群破坏影响下丘脑-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）表达来降低妊娠率。NRG1与星形胶质细胞ErbB2受体结合可升高前列腺素E2 （PGE2）和促性腺激素释放激素（GnRH），破坏HPO轴的稳态。此外，DEHP改变了肠道微生物群，破坏了微生物网络的稳定，并影响了β-葡萄糖醛酸酶相关的分类群，导致激素波动和生育能力降低。本研究强调肠道微生物群扰动是一种将DEHP暴露与生殖功能障碍联系起来的新机制。我们的研究提供了关于肠道微生物组和HPO轴的扰动及其功能的新见解，作为DEHP暴露干扰生殖功能相关人类健康的潜在新机制。

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来源期刊

npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology

CiteScore

12.10

自引率

3.30%

发文量

审稿时长

9 weeks

期刊介绍： npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.