Regulatory mechanism of matrix metalloproteinases in recurrent spontaneous abortion

Abstract

Objective To investigate the expression of matrix metalloproteinas (MMPs) in villi of patients with recurrent spontaneous abortion (RSA), and analyze the relationship and clinical significance between MMPs and RSA. Methods During February to May 2016 at Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, 24 patients with RSA were selected as RSA group, 26 healthy pregnant women in the same period were selected as control group, tumor necrosis factor (TNF)-α, interleukin (IL)-1β levels in plasma were measured by enzyme linked immunosorbent assay (ELISA). IL-1β, nuclear factor (NF)-κB, inhibitor of tumor necrosis factor(IκB)β, MMP-9 and MMP-2 were detected by RT-PCR, and the protein expression of MMP-9, MMP-2, NF-κB and IκBβ were detected by Western blotting. Results 1) The level of TNF-α in plasma of RSA group [(2.84±0.62) μg/L] was higher than that in control group [(1.32±0.43) μg/L] (P=0.047). 2) The expressions of TNF-α, NF-κB1, RelA and MMP-9 mRNA in villi of RSA group were significantly higher than those in control group (P<0.001, P<0.001, P=0.003, P<0.001), and the expression of IκBβ mRNA was significantly lower than that of control group (P=0.011). 3) The levels of MMP-9, NF-κB p65 and p50 protein in villi were significantly higher than those in control group (P=0.001, P=0.001, P<0.001), and the level of IκBβ protein in villi was significantly lower than that in control group (P<0.001). Conclusion The increase of TNF-α level in peripheral cells can affect the degradation of the protein of IκB in villi. The elevated expression of NF-κB increases the level of MMP-9, the excessive degradation of extracellular matrix in decidual leads to the shedding of embryo, and may induce miscarriage eventually. Key words: Spontaneous abortion; Chorionic villi; Matrix metalloproteinases; Recurrent spontaneous abortion