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

Abstract

ProblemAscending bacterial infection is associated with ∼ 40% of spontaneous preterm birth (PTB), and Ureaplasma spp. is one of the most common bacteria isolated from the amniotic fluid. Developing novel in vitro models that mimic in vivo uterine physiology is essential to study microbial pathogenesis. We utilized the feto‐maternal interface organ‐on‐chip (FMi‐OOC) device and determined the propagation of Ureaplasma parvum, and its impact on cell signaling and inflammation.Method of studyFMi‐OOC is a microphysiologic device mimicking fetal membrane/decidua interconnected through microchannels. The impact of resident decidual CD45+ leukocytes was also determined by incorporating them into the decidual chamber in different combinations with U. parvum. We tested the propagation of live U. parvum from the decidual to the amniochorion membranes (immunocytochemistry and quantitative PCR), determined its impact on cytotoxicity (LDH assay), cell signaling (JESSTM Western Blot), cellular transition (immunostaining for vimentin and cytokeratin), and inflammation (cytokine bead array).ResultsU. parvum transversed the chorion and reached the amnion epithelium after 72 hours but did not induce cell signaling kinases (p38MAPK and JNK) activation, or cellular transition (epithelial‐mesenchymal), regardless of the presence of immune cells. The inflammatory response was limited to the choriodecidual interface and did not promote inflammation in the amnion layer.ConclusionsOur data suggest that U. parvum is poorly immunogenic and does not produce massive inflammatory changes at the feto‐maternal interface. We speculate that the presence of U. parvum may still compromise the feto‐maternal interface making it susceptible to other pathogenic infection.

Cargo exchange between human and bacterial extracellular vesicles in gestational tissues: a new paradigm in communication and immune development

“…This can be compared to the EV cargo of BV/preterm birth-associated bacterial species such as Gardnerella vaginalis, GBS, and Ureaplasma spp. commonly isolated from the intrauterine/ intra-amniotic cavity [236,258,[262][263][264][265][266][267] .…”