adrenomedullin and Pregnancy--Ectopic

Ectopic pregnancy is the major cause of maternal morbidity and mortality in the first trimester of pregnancy. Tubal ectopic pregnancy (TEP) accounts for nearly 98% of all ectopic pregnancies. TEP is usually associated with salpingitis but the underlying mechanism in salpingitis leading to TEP remains unclear. Adrenomedullin (ADM) is a peptide hormone abundantly expressed in the fallopian tube with potent anti-inflammatory activities. Its expression peaks at the early luteal phase when the developing embryo is being transported through the fallopian tube. In the present study, we demonstrated reduced expression of ADM in fallopian tubes of patients with salpingitis and TEP. Using macrophages isolated from the fallopian tubes of these women, our data revealed that the salpingistis-associated ADM reduction contributed to aggravated pro-inflammatory responses of the tubal macrophages resulting in production of pro-inflammatory and pro-implantation cytokines IL-6 and IL-8. These cytokines activated the expression of implantation-associated molecules and Wnt signaling pathway predisposing the tubal epithelium to an adhesive and receptive state for embryo implantation. In conclusion, this study provided evidence for the role of ADM in the pathogenesis of TEP through regulating the functions of tubal macrophages.

Topics: Adrenomedullin; Adult; Biomarkers; Cell Line; Cell Plasticity; Cytokines; Disease Susceptibility; Embryo Implantation; Epithelium; Fallopian Tubes; Female; Gene Expression; Humans; Immunohistochemistry; Immunophenotyping; Macrophage Activation; Macrophages; Middle Aged; NF-kappa B; Pregnancy; Pregnancy, Ectopic; Receptors, Adrenomedullin; Salpingitis; Signal Transduction

Topics: Activins; ADAM12 Protein; Adrenomedullin; Biomarkers; CA-125 Antigen; Chorionic Gonadotropin, beta Subunit, Human; Creatine Kinase; Disintegrins; Fallopian Tube Diseases; Female; Glycodelin; Humans; Leukemia Inhibitory Factor; Membrane Proteins; Placental Lactogen; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Pregnancy-Specific beta 1-Glycoproteins; Pregnancy, Ectopic; Progesterone; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

To analyze the plasmatic ADM level in early pregnancy and to investigate the diagnostic value of ADM in early ectopic pregnancy (EP).. 70 patients with EP who had menopause for 5~8 weeks were included as study group, while 155 women with normal intrauterine pregnancy were also included as control group. The correlation between ADM level and menopause weeks was statistically analyzed and ROC curve was used to identify the diagnostic value of ADM.. (1) In 155 cases of normal intrauterine pregnancy, the plasmatic ADM level was increased with menopause weeks in linear relationship, and the correlation coefficient (R) was 0.991 (P<0.05). In 70 patients with EP, no significant increase was found with menopause weeks and no linear relationship can be found between ADM level and menopause weeks in EP group. The correlation coefficient (R) was 0.744 (P>0.05). (2) The multiple of median of plasmatic ADM level in EP group of menopause for 8 weeks was obviously lower than the intrauterine control group (P<0.01). (3) ROC curve was used to analyze the cut-off value of ADM level in the diagnosis of EP, and the area under the ROC curve was 0.523 (P>0.05) regardless of menopause weeks, however, the area under the ROC curve was 0.702 (P<0.05) at 8 weeks after menopause with sensitivity of 53.50% and specificity of 85.00%.. Different from normal intrauterine pregnancy, plasmatic ADM level in early EP was relatively lower and no significant increase was found with menopause weeks; further studies are still needed for plasmatic ADM level as an indicator in the early diagnosis of EP.

Topics: Adrenomedullin; Adult; Area Under Curve; Biomarkers; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Pregnancy; Pregnancy, Ectopic; ROC Curve; Sensitivity and Specificity