SFRP3 negatively regulates placental extravillous trophoblast cell migration mediated by the GCM1-WNT10B-FZD7 axis

What is it about?

Human extravillous trophoblast (EVT) cells are a group of specialized placental cells that migrate into uterine decidua to facilitate the establishment of blood circulation between mother and fetus. Poor or excessive EVT migration is associated with pregnancy complications, preeclampsia or placenta accreta. This study is intended to investigate how EVT cell migration is regulated and whether it is modulated by EVT-decidual cell interaction. Glial cells missing 1 (GCM1) transcription factor is essential for placental development and decreased GCM1 activity is detected in preeclampsia. Here we showed that GCM1 promotes trophoblast cell migration through a novel target gene, WNT10B. Moreover, WNT10B signaling stimulated cytoskeletal remodeling via the small GTPase Rac1 and frizzled 7 (FZD7) was identified as the cognate receptor for WNT10B to upregulate cell migration. We further showed that secreted frizzled-related protein 3 (SFRP3) is expressed in uterine decidual cells and that SFRP3 expression is elevated under decidualization stimuli and further enhanced by BMP2 via SMAD1. SFRP3 blocked the interaction between FZD7 and WNT10B to decrease trophoblast cell migration, which corroborated the elevated cell migration when co-cultured with SFRP3-knockdown decidual stromal cell monolayer. Therefore, the present study unravels novel EVT-decidual cell interaction controlling EVT cell migration, in which the GCM1-WNT10B-FZD7 axis promotes EVT cell migration and is negatively modulated by decidual SFRP3.

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