Placental-derived exosomes drive neural injury in CHORIO. To confirm whether cytokines themselves or placental-derived exosomes were able to induce brain CXCL1 expression, exosomes were isolated from CHORIO PCM (A). Exosomes from CHORIO placentae elevated CXCL1 mRNA in P2 brain slices (A - purple bar). Notably, cerebral CXCL1 mRNA levels were reduced by blockade of exosome release using the exosome generation inhibitor GW4869 (A - gray and black bars). Blockade of placental exosome generation also improved neural cell health and preserved developmental trajectory (B). Specifically, GABAARɣ2 mRNA was increased in P2 brain slices cultured with exosome depleted PCM compared to exosome containing PCM (B). (n = 4–5, two independent experiments, *p < 0.05, **p < 0.01, ***p < 0.001. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)