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-cervixdecidua-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.

Modeling an ascending infection by Ureaplasma parvum and its cell signaling and inflammatory response at the feto‐maternal interface

“…Studies about U. parvum have reported that they have poor immunogenicity, does not trigger a massive inflammatory response in human samples, and does not promote PTB in mouse models, which could be explained by this specie being a commensal of rodents, resulting in an immune response that may be different compared to humans 5,11,14 . Using the FMi‐OOC model, we tested the ascending infection of U. parvum and its pathogenic properties on the FMi.…”

“…These data support the systematic review and prior reports using fetal membrane explants and organ-on-a-chip devices. 5,10,14…”

“…10 Similar conclusions were made on ascending infection and PTB using animal model studies. 13,14 Conversely, direct administration of U. parvum into the amniotic fluid can cause PTB suggesting that feto-maternal interface (FMi) is a major barrier for the propagation of a load of microbe needed to reach the amniotic cavity to cause a fetal inflammatory response needed to drive parturition signals. 15 The cell signaling associated with infection that leads to adverse gestational outcomes has also been studied in recent years.…”

“…Here, multiple cell types can be cultured in an interconnected multiwell device mimicking an organ system as seen in utero. [21][22][23] Our group has established several models of OOC recently, 14,[24][25][26] and the fetal membrane feto-maternal interface organ-on-chip (FMi-OOC) 27 recreated both maternal (i.e., decidua) and fetal sides (i.e., amniochorion). This model has been used…”

Ventral hernia repair surgery after abdominal gunshot wound

“…It contributes to an extreme rise in the frequency of gunshot wounds resulting in severe destruction of abdominal organs (most often the small intestine at 50 %, the large intestine at 40 %, the liver at 40 %, and the intra-abdominal vascular system at 30 %), which is accompanied by peritonitis and the further development of different complications (anastomotic leakage, formation of abscesses, repeated bleeding, etc.). Such conditions require repeated surgical interventions, which contribute to the formation of postoperative ventral hernias [34,36,37,38]. The surgical management of ventral hernias is challenging due to severe adhesion in the abdominal cavity (irrespective of the time period since the injury and the last surgical interventions), the difficulties in closing massive defects of the muscle-aponeurotic component of the anterior abdominal wall, contracture of the anterior abdominal wall, and the development of the abdominal compartment syndrome in the postoperative period.…”