NCOA2-induced secretion of leptin leads to fetal growth restriction via the NF-κB signaling pathway.

Background: Fetal growth restriction (FGR) is one of the most common fetal complications during pregnancy in the obstetrics department, with poor therapeutic efficacy. The local inflammatory response of the placenta has gradually become known as the main mechanism for the occurrence and development of FGR. The aim of this study was to improve the knowledge of placental inflammatory response mechanisms in regulating gene expression.

Methods: The differentially expressed genes (DEGs) in FGR patients were analyzed through bioinformatics analysis. The expression of gene level was detected by immunohistochemistry (IHC) staining, quantitative polymerase chain reaction (qPCR), or enzyme-linked immunosorbent assay (ELISA). The proliferation, migration, and apoptosis of HTR-8/SVneo trophoblast cells stimulated with lipopolysaccharide (LPS) was performed by Cell Counting Kit-8 (CCK-8) assay, clone formation assay, Transwell assay, and flow cytometry. The mechanisms of gene expression in regulating placental inflammatory response were elucidated by western blotting.

Results: Nuclear receptor coactivator 2 () was identified as a very critical gene in the progression of FGR by bioinformatics analysis and the expression of was shown to be down-regulated in FGR patients. Overexpression of promoted the proliferation, migration, and inhibited apoptosis and pro-inflammatory cytokines secretion in HTR-8/SVneo trophoblast cells stimulated with LPS via the nuclear factor (NF)-κB pathway. In addition, leptin was increased in both tissue and peripheral blood samples of FGR patients, and overexpression of inhibited the secretion of leptin in HTR-8/SVneo trophoblast cells stimulated with LPS.

Conclusions: All these findings suggest that -induced secretion of leptin leads to FGR progression via the NF-κB pathway and provides a clinical therapeutic target in FGR and a potent marker for the identification of FGR.