angiotensinogen and Abortion--Habitual

Recurrent miscarriage (RM) affects 5% of women, it has an adverse emotional impact on women. Because of the complexities of early development, the mechanism of recurrent miscarriage is still unclear. We hypothesized that abnormal placenta leads to early recurrent miscarriage (ERM). The aim of this study was to identify ERM associated factors in human placenta villous tissue using proteomics. Investigation of these differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying recurrent miscarriage (RM).. To gain more insight into mechanisms of recurrent miscarriage (RM), a comparative proteome profile of the human placenta villous tissue in normal and RM pregnancies was analyzed using iTRAQ technology and bioinformatics analysis used by Ingenuity Pathway Analysis (IPA) software.. In this study, we employed an iTRAQ based proteomics analysis of four placental villous tissues from patients with early recurrent miscarriage (ERM) and four from normal pregnant women. Finally, we identified 2805 proteins and 79,998 peptides between patients with RM and normal matched group. Further analysis identified 314 differentially expressed proteins in placental villous tissue (≥1.3-fold, Student's t-test, p < 0.05); 209 proteins showed the increased expression while 105 proteins showed decreased expression. These 314 proteins were analyzed by Ingenuity Pathway Analysis (IPA) and were found to play important roles in the growth of embryo. Furthermore, network analysis show that Angiotensinogen (AGT), MAPK14 and Prothrombin (F2) are core factors in early embryonic development. We used another 8 independent samples (4 cases and 4 controls) to cross validation of the proteomic data.. This study has identified several proteins that are associated with early development, these results may supply new insight into mechanisms behind recurrent miscarriage.

Topics: Abortion, Habitual; Adult; Angiotensinogen; China; Chorionic Villi; Cluster Analysis; Computational Biology; Embryonic Development; Female; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Regulatory Networks; Humans; Mitogen-Activated Protein Kinase 14; Placenta; Placentation; Pregnancy; Pregnancy Trimester, First; Proteomics; Prothrombin; Software

The objective of this study was to determine whether or not the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AT1R), and angiotensinogen (AGT) gene polymorphisms are associated with idiopathic recurrent spontaneous abortions (RSAs) in Korean women.. A total of 251 patients with unexplained consecutive pregnancy losses, and 126 healthy controls with at least one live birth and no history of pregnancy loss.. The odds ratios (ORs) of the ACE ID (OR=2.423; 95% confidence interval (CI)=1.417-4.142; p=0.001) and the ACE II (OR=2.050; 95% CI=1.143-3.675; p=0.018) for the ACE DD genotype were significantly different between patients with idiopathic RSA and controls; however, there were no significant differences between patients and controls with respect to the AT1R 1166A>C and AGT M235T polymorphisms. In a haplotype-based analysis of I-A (p=0.010), D-A (p=0.004), I-A-T (p=0.033), D-A-T (p=0.0005), and D-C-T (p=0.013) polymorphism pairs with synergistic effects derived by the MDR method in patients and in controls showed significant results.. This study suggests that ACE, AT1R and AGT polymorphisms and haplotypes are a genetic determinant for the risk of idiopathic RSA in Korean women.

Topics: Abortion, Habitual; Adult; Angiotensinogen; Female; Haplotypes; Humans; Middle Aged; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Pregnancy; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Republic of Korea; Risk Factors; Young Adult

Recurrent spontaneous abortion (RSA), defined as the loss of three or more consecutive pregnancies prior to the 20th week of gestation, affects up to 5% of the child-bearing population. To investigate the proteins associated with RSA, the protein expression in human follicular fluid was analyzed using 2-DE. Follicular fluid contains a variety of biologically important proteins for oocyte fertilization and follicle maturation in the mammalian reproductive process. Therefore, it can be used as a provisional source for identifying proteins involved in RSA. In this study, we identified five aberrantly expressed proteins (complement component C3c chain E, fibrinogen gamma, antithrombin, angiotensinogen, and hemopexin precursor) in follicular fluid from RSA patients with MALDI-TOF-MS and nano-LC MS/MS. Western blot analysis confirmed that the protein expression level of fibrinogen gamma and antithrombin was less in follicular fluid from RSA patients than those from normal controls. Semiquantitative RT-PCR and real-time PCR analyses revealed that mRNA level of these coagulation factors was also decreased significantly in chorionic villi of RSA patients compared with normal samples. Taken all together, it is likely that coagulation factors (fibrinogen gamma and antithrombin) play an important role in maintaining the normal pregnancy.

Topics: Abortion, Habitual; Adult; Angiotensinogen; Antithrombins; Chorionic Villi; Complement C3c; Down-Regulation; Electrophoresis, Gel, Two-Dimensional; Female; Fibrinogen; Follicular Fluid; Hemopexin; Humans; Proteomics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Interleukin (IL)-1beta, angiotensinogen (Agt), and endothelium-derived nitric oxide synthase (eNOS) are thought to be involved in idiopathic recurrent miscarriage (IRM). We investigated the correlation between IRM and common polymorphisms in Agt, Nos3 and IL-1beta genes: one polymorphism in the promoter region of the IL-1beta gene, one in exon 2 of the Agt gene, and one in exon 7 of the Nos3 gene. A total of 130 women with a history of IRM and 67 healthy control women were included in the study. Genotyping for the C/T transition at position -511 in the promoter region of IL1B, for the single base M235T polymorphism of Agt, and for the missense Glu298Asp variant of Nos3 was performed using PCR, an allele-specific oligonucleotide hybridization assay, and pyrosequencing, respectively. Allele and genotype frequencies of all polymorphisms were similar among women with IRM and controls. Between women with primary and secondary recurrent miscarriages, no statistically significant differences between allele and genotype frequencies were observed. Despite promising experimental data, our data fall short of showing any significant association between a variant of the promoter region of IL1B, the M235T polymorphism of Agt, and the Glu298Asp missense variant of Nos3 and the occurrence of IRM.

Topics: Abortion, Habitual; Adult; Angiotensinogen; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Interleukin-1; Mutation, Missense; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Pregnancy; Promoter Regions, Genetic