Fig. 1: Human chorio-decidual interface-on-chip (CDi-on-chip).

A Conceptual framework of how the chorio-decidual interface responds to maternal insults. We hypothesize that the decidua and resident innate immune cells counter maternal insults by promoting inflammation, while the chorion produces immunoregulatory molecules such as HLA-G and PGRMC2. With intact barrier functions, the insult should resolve without causing fetal inflammatory response. When HLA-G or PGRMC2 is compromised, this should result in excessive inflammatory response that may lead to premature labor activation. B Schematic diagram of the chorio-decidual interface-on-chip and treatments. Both (A) and (B) are created with BioRender.com. C Immune cell subpopulations in the decidua parietalis at term prior to labor (n = 3) based on Mosebarger et al. ³⁶. D Phase-contrast images of the CDi-on-chip. Yellow arrowheads point to cell line-derived immune cells. E Immunostaining of CD45 (red) and vimentin (green) expression of cells in the CDi-on-chip. DAPI (blue) was used for nuclear staining. Separation between two chambers is highlighted in yellow dashed circle. Inset images show migrating and migrated cell line-derived immune cells (yellow arrowheads). F Timelapse stills at a device microchannel with a cell line-derived immune cell (yellow arrowhead) migrating towards CTC. Scale bar for (D–F), 100 µm. ROS: reactive oxygen species, NK: natural killer, HLA-G: human leukocyte antigen G, PGRMC2: progesterone receptor membrane component 2, CTC: chorion trophoblast cell, DEC: decidual cell, CD45: cluster of differentiation 45, LPS: lipopolysaccharide, pIC: poly(I:C), mOS: maternal oxidative stress.