Ascending infection of Gardnerella spp. and compartmentalized inflammatory response in fetal-maternal interface organ-on-chip model.

Abstract

Preterm birth is a leading cause of neonatal morbidity and mortality worldwide, with ascending infection and inflammation at the fetal-maternal interface recognized as major contributors to its pathophysiology. Gardnerella spp., key species associated with bacterial vaginosis, have been implicated in adverse pregnancy outcomes; however, the mechanisms underlying their ability to ascend and trigger inflammatory responses remain poorly understood. In this study, we used a fetal-maternal interface organ-on-chip model to investigate the ascending infection of Gardnerella spp. and the resulting compartmentalized cytokine response. The device integrated decidual, chorionic trophoblast, amniotic mesenchymal and amniotic epithelial cells to mimic the in vivo architecture of the fetal membranes. Quantitative PCR revealed progressive bacterial ascension, with a significantly higher load of Gardnerella spp. in the amnion mesenchymal layer after 48 h of stimulation. Cytokine analysis demonstrated increased production of interleukin (IL)-1β, IL-6, C-X-C motif chemokine ligand 8 and IL-10 across cellular compartments, indicating a coordinated pro-inflammatory and compensatory anti-inflammatory response. These findings provide direct evidence of Gardnerella spp. invasion dynamics and immune activation at the fetal-maternal interface, supporting the use of microphysiological systems as translational tools to study infection-driven mechanisms of spontaneous preterm birth. KEY POINTS: Gardnerella spp. ascend rapidly across the fetal-maternal interface. Ascending infection induces compartmentalized inflammatory cytokine responses. Amnion mesenchymal cells exhibited the highest bacterial burden after 48 h. The fetal-maternal interface organ-on-chip provides a translational model for studying infection-driven preterm birth.