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连接人类子宫颈和阴道芯片中的宫颈黏液可调节阴道微生物群失调。

Cervical mucus in linked human Cervix and Vagina Chips modulates vaginal dysbiosis.

作者信息

Gutzeit Ola, Gulati Aakanksha, Izadifar Zohreh, Stejskalova Anna, Rhbiny Hassan, Cotton Justin, Budnik Bogdan, Shahriar Sanjid, Goyal Girija, Junaid Abidemi, Ingber Donald E

机构信息

Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA USA.

Department of Obstetrics and Gynecology, IVF Unit, Rambam Medical Center, Haifa, Israel.

出版信息

NPJ Womens Health. 2025;3(1):5. doi: 10.1038/s44294-025-00054-2. Epub 2025 Jan 29.

DOI:10.1038/s44294-025-00054-2
PMID:39896100
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11779628/
Abstract

This study explores the protective role of cervicovaginal mucus in maintaining vaginal health, particularly in relation to bacterial vaginosis (BV), using organ chip technology. By integrating human Cervix and Vagina Chips, we demonstrated that cervical mucus significantly reduces inflammation and epithelial damage caused by a dysbiotic microbiome commonly associated with BV. Proteomic analysis of the Vagina Chip, following exposure to mucus from the Cervix Chip, revealed differentially abundant proteins, suggesting potential biomarkers and therapeutic targets for BV management. Our findings highlight the essential function of cervical mucus in preserving vaginal health and underscore the value of organ chip models for studying complex interactions within the female reproductive tract. This research provides new insights into the mechanisms underlying vaginal dysbiosis and opens avenues for developing targeted therapies and diagnostic tools to enhance women's reproductive health.

摘要

本研究利用器官芯片技术探讨宫颈阴道黏液在维持阴道健康,特别是与细菌性阴道病(BV)相关方面的保护作用。通过整合人宫颈芯片和阴道芯片,我们证明宫颈黏液能显著减轻由通常与BV相关的生态失调微生物群引起的炎症和上皮损伤。对暴露于宫颈芯片黏液后的阴道芯片进行蛋白质组分析,发现了丰度有差异的蛋白质,提示了BV管理的潜在生物标志物和治疗靶点。我们的研究结果突出了宫颈黏液在维护阴道健康中的重要功能,并强调了器官芯片模型在研究女性生殖道内复杂相互作用方面的价值。这项研究为阴道生态失调的潜在机制提供了新见解,并为开发针对性疗法和诊断工具以促进女性生殖健康开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/cde88a642096/44294_2025_54_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/5a7a7f7ef3dd/44294_2025_54_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/c320f64b10d1/44294_2025_54_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/1a79077b7a2c/44294_2025_54_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/ccf333b23205/44294_2025_54_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/cde88a642096/44294_2025_54_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/5a7a7f7ef3dd/44294_2025_54_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/c320f64b10d1/44294_2025_54_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/1a79077b7a2c/44294_2025_54_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/ccf333b23205/44294_2025_54_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60d0/11779628/cde88a642096/44294_2025_54_Fig5_HTML.jpg

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本文引用的文献

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2
Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip.人源阴道芯片模型中的阴道微生物组-宿主相互作用。
Microbiome. 2022 Nov 26;10(1):201. doi: 10.1186/s40168-022-01400-1.
3
The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest.
2023 年的 STRING 数据库:针对任何感兴趣的测序基因组的蛋白质-蛋白质关联网络和功能富集分析。
Nucleic Acids Res. 2023 Jan 6;51(D1):D638-D646. doi: 10.1093/nar/gkac1000.
4
eIF4A3 Promotes RNA Viruses' Replication by Inhibiting Innate Immune Responses.eIF4A3 通过抑制先天免疫反应促进 RNA 病毒的复制。
J Virol. 2022 Nov 23;96(22):e0151322. doi: 10.1128/jvi.01513-22. Epub 2022 Oct 31.
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DDR1 functions as an immune negative factor in colorectal cancer by regulating tumor-infiltrating T cells through IL-18.DDR1 通过调节肿瘤浸润 T 细胞来发挥免疫负因子的作用,从而调控结直肠癌中的 IL-18。
Cancer Sci. 2022 Nov;113(11):3672-3685. doi: 10.1111/cas.15533. Epub 2022 Aug 24.
6
Cysteine dependence of Lactobacillus iners is a potential therapeutic target for vaginal microbiota modulation.乳杆菌属的半胱氨酸依赖性是阴道微生物组调节的一个潜在治疗靶点。
Nat Microbiol. 2022 Mar;7(3):434-450. doi: 10.1038/s41564-022-01070-7. Epub 2022 Mar 3.
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Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia.宫颈上皮内瘤变手术后宫颈阴道微生物群和宫颈细胞因子谱的变化。
Sci Rep. 2021 Jan 25;11(1):2156. doi: 10.1038/s41598-020-80176-6.
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The Association Between Vaginal Microbiota Dysbiosis, Bacterial Vaginosis, and Aerobic Vaginitis, and Adverse Pregnancy Outcomes of Women Living in Sub-Saharan Africa: A Systematic Review.撒哈拉以南非洲地区女性阴道微生物失调、细菌性阴道病和需氧性阴道炎与不良妊娠结局的相关性:系统评价。
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