title: Expression of GRIM-19 in missed abortion and possible pathogenesis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Villous samples were collected from a total of 50 women with missed abortion and 50 women with normal pregnancies.
  
  
  METHODS
  Villous samples from the missed-abortion group were collected by curettage or manual vacuum aspiration. The control villous samples were obtained by vacuum aspiration.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 villi from 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.
  
  
  CONCLUSIONS
  The GRIM-19 deficiency in the villus may be associated with missed abortion via increasing apoptosis and affecting angiogenesis.
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Deng
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China. Electronic address: qlszcl@163.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Chao
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Infertility Center, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000030:Abortion, Missed / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D002824:Chorionic Villi / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D011247:Pregnancy; D015995:Prevalence; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human
keywords: GRIM-19; angiogenesis; apoptosis; missed abortion; mitochondria