Chemerin facilitates placental trophoblast invasion and spiral artery remodeling through the pentose phosphate pathway.

AIMS: The invasion of trophoblasts and remodeling of spiral arteries are the requisite processes for successful placentation. A defect of trophoblast invasion is closely associated with pregnancy complications, including miscarriage and preeclampsia. In this study, we investigated the function of chemerin in trophoblast invasion and artery remodeling and explored the underlying mechanism in this process.

MAIN

METHODS

Immunostaining was performed to examine chemerin expression in different days of mouse placenta and early stage of human placenta. Chemerin KO and LPS-treated mice, with exogenous chemerin peptide, were used to evaluate trophoblast giant cells (TGC) invasion, artery remodeling, and NK cell infiltration. Chemerin KO and LPS-treated decidua on E8.5 were conducted in metabolites file and measured related enzymes' expression. Chemerin's function was further examined by human trophoblast HTR-8 cell migration and the enzymes expression in the pentose phosphate pathway.

KEY FINDINGS: Chemerin has high expression in mouse-invasive TGC and human extra-villous trophoblast cells. Deficiency of chemerin and LPS treatment in pregnant mice impaired placental TGC invasion, spiral artery remodeling, and NK cell infiltration in decidua, which mainly attributed to the downregulation of metabolites and G6PD and RPIA expression in pentose phosphate pathway (PPP). Chemerin activated the PPP to accelerate HTR-8 cell migration. Exogenous chemerin administration remarkably attenuated the defect of TGC invading and artery remodeling in LPS-treated mice, and promoted NK infiltration and maternal blood perfusion.

SIGNIFICANCE: This study described the indispensable role of chemerin in trophoblast invasion and arterial remodeling, and suggested its potential application in pregnancy complications miscarriage and preeclampsia.