Chemerin sustains the growth of spongiotrophoblast and sinusoidal trophoblast giant cells through fatty acid oxidation
Background Placental metabolic abnormalities are linked to pregnancy complications such as preeclampsia, gestational diabetes mellitus, and fetal growth restriction. However, little is known about how the metabolic processes regulate placental development and trophoblast differentiation. The adipokine chemerin has elevated serum levels in pregnant women and regulates placental lipid metabolism, potentially playing a role in both placental development and trophoblast differentiation. Results In this study, we observed the increased chemerin expression on the serum and placenta from the pregnant mice. Chemerin is highly expressed in the extraembryonic primary parietal trophoblast giant cells and the ectoplacental cone (EPC) trophoblast cells. Excessive chemerin treatment in mice results in the increased placental lipid accumulation, promotes the expansion of glycogen trophoblast cell (GlyT) and syncytiotrophoblast, and restricts the growth of spongiotrophoblast (SpT) and sinusoidal trophoblast giant cell (S-TGC). Chemerin deficiency led to increased expression of placental fatty acid oxidation enzymes and disrupted the proliferation of SpT and S-TGC in the labyrinth. Furthermore, we utilized the fatty acid oxidation inhibitor etomoxir, demonstrated that blocking fatty acid oxidation hinders the proliferation of SpT and S-TGC in the labyrinth. Conclusions Our study demonstrated that chemerin-related lipid metabolism is crucial for EPC trophoblast differentiation during placental development, providing evidence that chemerin determines the growth of SpT and S-TGC through fatty acid oxidation. These findings also imply a possible pathological mechanism for pregnancy complications associated with chemerin. Overall design: RNA-seq profiling of  placentas from C57BL/6 Wild type mice (4mice) and chemerin knockout mice(4 mice)  at embryonic day 18.5