Expression of GRIM-19 in missed abortion and possible pathogenesis

Abstract

To study the expression of a gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the villi of patients with missed abortion and possible pathogenesis. Case-control study. University hospital. Villous samples were collected from a total of 50 women with missed abortion and 50 women with normal pregnancies. Villous samples from the missed-abortion group were collected by curettage or manual vacuum aspiration. The control villous samples were obtained by vacuum aspiration. Protein and messenger RNA levels of GRIM-19 in villous samples were measured by Western blot and real-time polymerase chain reaction, and the location of GRIM-19 in trophoblasts was detected by immunohistochemistry. Apoptotic cells and microvessel density in villous sample were assayed by TUNEL and immunostaining. Mitochondrial membrane potential and apoptotic changes of the HTR-8/SVneo cell line in response to down-regulation of GRIM-19 were evaluated by 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide and annexin V/propidium iodide. Vascular endothelial growth factor production was measured by ELISA. GRIM-19 protein and messenger RNA levels in the villi from women with missed abortion were found to be significantly lower than in women who had normal pregnancies. Many more apoptotic cells and lower microvessel density were detected in villifrom patients with missed abortion. Knockdown of GRIM-19 in HTR-8/SVneo cells gave rise to a collapse of mitochondrial membrane potential and increase in apoptosis. Simultaneously, the vascular endothelial growth factor secretion in the HTR-8/SVneo cells culture medium decreased as GRIM-19 became down-regulated. The GRIM-19 deficiency in the villus may be associated with missed abortion via increasing apoptosis and affecting angiogenesis.