@article{bibcite_8251,
  keywords = {Ureaplasma parvum infection of the maternal uterine tract, microfluidics, mycoplasma, organ-on-a-chip, Pregnancy, Preterm birth},
  author = {Ourlad Alzeus G. Tantengco and Lauren S. Richardson and Enkhtuya Radnaa and Ananth Kumar Kammala and Sungjin Kim and Paul Mark B. Medina and Arum Han and Ramkumar Menon},
  title = {Modeling ascending Ureaplasma parvum infection through the female reproductive tract using vagina-cervix-decidua-organ-on-a-chip and feto-maternal interface-organ-on-a-chip},
  abstract = {Genital mycoplasmas can break the cervical barrier and cause intraamniotic infection and preterm birth. This study developed a six-chamber vagina-cervix-decidua-organ-on-a-chip (VCD-OOC) that recapitulates the female reproductive tract during pregnancy with culture chambers populated by vaginal epithelial cells, cervical epithelial and stromal cells, and decidual cells. Cells cultured in VCD-OOC were characterized by morphology and immunostaining for cell-specific markers. We transferred the media from the decidual cell chamber of the VCD-OOC to decidual cell chamber in feto-maternal interface organ-on-a-chip (FMi-OOC), which contains the fetal membrane layers. An ascending Ureaplasma parvum infection was created in VCD-OOC. U. parvum was monitored for 48 h post-infection with their cytotoxicity (LDH assay) and inflammatory effects (multiplex cytokine assay) in the cells tested. An ascending U. parvum infection model of PTB was developed using CD-1 mice. The cell morphology and expression of cell-specific markers in the VCD-OOC mimicked those seen in lower genital tract tissues. U. parvum reached the cervical epithelial cells and decidua within 48 h and did not cause cell death in VCD-OOC or FMi-OOC cells. U. parvum infection promoted minimal inflammation, while the combination of U. parvum and LPS promoted massive inflammation in the VCD-OOC and FMi-OOC cells. In the animal model, U. parvum vaginal inoculation of low-dose U. parvum did not result in PTB, and even a high dose had only some effects on PTB (20\%). However, intra-amniotic injection of U. parvum resulted in 67\% PTB. We report the colonization of U. parvum in various cell types; however, inconsistent, and low-grade inflammation across multiple cell types suggests poor immunogenicity induced by U. parvum.},
  year = {2022},
  journal = {The FASEB Journal},
  volume = {36},
  pages = {e22551},
  month = {2022},
  issn = {1530-6860},
  url = {https://onlinelibrary.wiley.com/doi/abs/10.1096/fj.202200872R},
  doi = {10.1096/fj.202200872R},
  language = {en},
}