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Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids

  • General Gynecology: Original Article
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Abstract

To facilitate in vitro mechanistic studies in pelvic inflammatory disease and subsequent tubal factor infertility, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae. The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in Fannyhessea vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. In summary, we have shown that patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful in vitro model system to study the host-pathogen interaction during bacterial infection.

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Funding

The study was funded by Akiko Yamazaki and Jerry Yang Faculty Scholar Fund in Pediatric Translational Medicine, Stanford Maternal and Child Health Research Institute (to BY), NIH K08CA222835 (to BY), NIH R01AI139189 (to CLH, DNF, BY), Women’s Cancer Innovation Award, Stanford Cancer Institute (to BY), and the Dunlevie Maternal-Fetal Medicine Center for Discovery, Innovation and Clinical Impact at Stanford University (to BY).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Stanford University School of Medicine, 240 Pasteur Drive, Stanford, CA, 94305, USA

    Bo Yu

  2. Stanford Maternal & Child Health Research Institute, Stanford University School of Medicine, Stanford, CA, USA

    Bo Yu

  3. Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA

    Bo Yu

  4. Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA

    Stephen McCartney

  5. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. North, E4-100, Seattle, WA, 98109, USA

    Susan Strenk, Daniel J. Valint, Congzhou Liu & David N. Fredricks

  6. Department of Epidemiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Catherine L. Haggerty

  7. Department of Medicine, University of Washington, Seattle, WA, USA

    David N. Fredricks

Authors
  1. Bo Yu
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  2. Stephen McCartney
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  3. Susan Strenk
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  4. Daniel J. Valint
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  5. Congzhou Liu
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  6. Catherine L. Haggerty
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  7. David N. Fredricks
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Contributions

BY conceived and designed the study and drafted the manuscript. BY, SM, SS, DV, and CL collected and analyzed the data. BY, CLH, and DNF obtained funding and edited the manuscript. All authors have read and approved the final manuscript.

Corresponding authors

Correspondence to Bo Yu or David N. Fredricks.

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Fallopian tube organoids respond to acute infection with upregulation of inflammatory genes specific to different vaginal bacterial species.

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Yu, B., McCartney, S., Strenk, S. et al. Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids. Reprod. Sci. 31, 505–513 (2024). https://doi.org/10.1007/s43032-023-01350-5

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  • DOI: https://doi.org/10.1007/s43032-023-01350-5

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