Saving placental thrombomodulin

In this issue of Blood, Kohli et al(1) report a noncoagulation role of thrombo-modulin (TM) expressed on trophoblast cells in maintaining placental growth and healthy embryogenesis. They show that (1) the inflammatory cytokine interleukin-1 beta (IL-1 beta) suppressed TM synthesis from trophoblast stem cells in culture and induced the ectodomain shedding of TM from these cells; (2) the TM shedding was also induced in pregnant C57BL/6J mice infused with endothelial cell-derived extracellular vesicles (eEVs), which cause placental inflammation; (3) the IL-1 beta receptor antagonist anakinra prevented TM shedding in these eEV-infused pregnant mice and reduced placental abnormalities in these mice; (4) the soluble TM that resists proteolysis and oxidation (solulin) reduced TM shedding in the pregnant C57BL/6J mice infused with eEVs and prevented fetal death, intrauterine growth restriction, placental inflammation, and growth suppression; and (5) the protection offered by solulin was reproduced in transgenic mice with enhanced expression of TM in embryonic tissue, including trophoblasts. The key findings from the pregnant mice were reproduced in well-controlled in vitro experiments using trophoblastic stem cells in culture and further validated by studying placentas collected from patients with preeclampsia.

Automated summary

The study reveals a noncoagulation role of TM in maintaining placental growth and healthy embryogenesis, with IL-1 beta playing a key role in regulating TM synthesis and shedding. Solulin shows potential in preventing TM shedding and related abnormalities.