Abstract

Preeclampsia (PE) is a severe pregnancy disorder caused by placental dysfunction. Protein O-fucosylation is a type of protein post translational modification that is catalyzed by protein O-fucosyltransferases (poFUTs). However, the role and underlying mechanisms of O-fucosylation/poFUT1 in PE remain elusive. Here, we revealed a lower level of poFUT1 in the plasma and placental tissues of PE patients than in normal pregnancy (NP) women. Moreover, poFUT1 deletion induced PE-like phenotypes in a mouse model. Mechanistically, we globally screened O-fucosylated proteins and identified EDIL3 with an O-fucosylation site at threonine 88. Furthermore, O-fucosylation-EDIL3 can directly interact with LIFR on trophoblasts, consequently activating the STAT3 signaling pathway, promoting the invasion and vascular remodeling ability of trophoblasts. Conversely, de-O-fucosylation-EDIL3 aggravated PE-like phenotypes by attenuating placental development in vitro and in vivo. Our data elucidate the function of poFUT1/O-fucosylation EDIL3/LIFR axis during placental development, providing glycol-based target for diagnostic and therapeutic of preeclampsia.