02761nas a2200313   4500000000100000000000100001008004100002260000900043653006200052653001800114653001500132653002000147653001400167653001800181100003100199700002500230700002000255700002500275700001600300700002400316700001300340700001900353245017700372856006600549300001100615490000700626520180000633022001402433       2022                            d  c202210aUreaplasma parvum infection of the maternal uterine tract10amicrofluidics10amycoplasma10aorgan-on-a-chip10aPregnancy10aPreterm birth1 aOurlad Alzeus G. Tantengco1 aLauren S. Richardson1 aEnkhtuya Radnaa1 aAnanth Kumar Kammala1 aSungjin Kim1 aPaul Mark B. Medina1 aArum Han1 aRamkumar Menon00aModeling 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  uhttps://onlinelibrary.wiley.com/doi/abs/10.1096/fj.202200872R  ae225510 v363 aGenital 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.  a1530-6860