Why does the fallopian tube fail in ectopic pregnancy? The role of activins, inducible nitric oxide synthase, and MUC1 in ectopic implantation.

OBJECTIVE: To investigate the role of activin-ßA subunit, activin type II receptors, inducible nitric oxide synthase (iNOS), and MUC1 in the pathogenesis of ectopic pregnancy (EP) and their involvement in the determination of the implantation site. DESIGN: Observational study. SETTING: Academic unit of reproductive and developmental medicine. PATIENT(S): Four women at the luteal phase, three pseudopregnant women at the time of hysterectomy for benign disease, and 10 archived cases of EP. We collected 14 Fallopian tubes were collected from four women at the luteal phase and three pseudopregnant women at the time of hysterectomy for benign disease; specimens from implantation site, trophoblast and remote sites from the implantation site were collected from 10 archived cases of EP. INTERVENTION(S): Immunohistochemistry and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME MEASURE(S): Comparison of the expression of candidate molecules between the different groups. RESULT(S): The expression of activin-ßA subunit, activin type II receptors, and iNOS was statistically significantly increased and expression of MUC1 statistically significantly decreased in tubes bearing an EP. There was no statistically significant difference in the expression of the candidate molecules between the implantation and remote sites. Candidate molecules were also expressed in the trophoblast. CONCLUSION(S): The pathological expression of candidate molecules by tubes bearing an EP is not involved in the determination of implantation site. Additionally, candidate molecules may play a role in the regulation of trophoblast cells in vivo during early pregnancy.

Cyclic and characteristic expression of phosphorylated Akt in human endometrium and decidual cells in vivo and in vitro.

BACKGROUND: Akt is activated by phosphorylation and plays an important role in cell survival and maintenance of structure. METHODS: We investigated whether phosphorylated Akt was characteristically expressed in human endometrium in vivo and whether insulin-like growth factor-I (IGF-I) can activate Akt using cultured decidualized human stromal cells in vitro, using immunohistochemistry and Western blotting analysis. RESULTS: The levels of phosphorylated Akt protein increased markedly in the decidual tissues from ectopic pregnancy. The expression of phosphorylated Akt protein in stromal cells increased with the decidualization. The decidual cells showed strong cytoplasmic staining for phosphorylated Akt. However, cultured decidualized human stromal cells diminished phosphorylated Akt expression compared to control cells. IGF-I administration to decidualized human stromal cells significantly recovered pAkt expression. The effect of IGF-I on decidualized human stromal cells was blocked by an inhibitor of phosphatidylinositol-3 kinase (PI3K) (LY294,002). These results suggest that IGF-I may activate Akt via PI3K in human endometrium and decidua. The expression of phosphorylated Akt in stromal cells was only detected in the functional layer, where tissue remodelling occurs during menstruation or implantation. CONCLUSIONS: Akt activation may be involved in cell survival and extracellular matrix remodelling in human endometrium and decidua.

Serum levels of myoglobin, creatine phosphokinase, and smooth muscle heavy-chain myosin in patients with ectopic pregnancy.

STUDY OBJECTIVE: Serum markers of smooth muscle destruction have been shown to be elevated in ectopic pregnancy, but they remain of questionable clinical utility. Our goal was to determine the clinical utility of 3 markers of smooth muscle destruction: creatine phosphokinase (CPK), smooth muscle heavy-chain myosin (SMHC), and myoglobin. METHODS: This was a prospective cohort study, with consecutive enrollment of all women in the first trimester of pregnancy who presented to our urban emergency department with complaints of lower abdominal pain, vaginal bleeding, or both. Patients were excluded from the study if there was a history of recent surgery or major trauma. Data analysis included receiver operating characteristic (ROC) curve, 95% confidence intervals (CIs), and a regression model. RESULTS: A total of 378 patients were enrolled, with 61 patients diagnosed with an ectopic pregnancy, and 317 patients placed in the non-ectopic pregnancy group with other diagnoses. ROC curve analysis revealed an area under the curve of 0.56 (95% CI 0.51 to 0.61) for CPK, 0.63 (95% CI 0.59 to 0.68) for SMHC, and 0.58 (95% CI 0.53 to 0.63) for myoglobin. A regression model analyzing the effects of race, maternal age, estimated gestational age, and serum levels of human chorionic gonadotropin beta-subunit found no significant confounders. CONCLUSION: Although there is a statistically significant elevation in the serum levels of SMHC, the range of values seen is too large to allow SMHC to be a useful screening tool.

Is maternal serum creatine kinase actually a marker for early diagnosis of ectopic pregnancy?

OBJECTIVE: Our purpose was to investigate whether serum creatine kinase (CK) levels could be used as an early marker of ectopic pregnancy. Student's t-test was used for statistical analysis. STUDY DESIGN: In a prospective study we therefore measured serum progesterone, beta hCG and CK levels in 30 women with ectopic pregnancies, 30 women with ongoing pregnancies and 30 women with missed abortion. RESULTS: The mean serum CK concentration for patients with an ectopic pregnancy, ongoing pregnancy, and the women with missed abortion was 81.4 +/- 66.2, 81.5 +/- 40.3, 84.8 +/- 49.3, respectively. No relationship was found between CK level and the location of the pregnancy. CONCLUSION: Conversely to the first report of Lavie et al. (Am J Obstet Gynecol 1993; 169: 1149), our data suggest that serum CK level is not discriminative in the early diagnosis of tubal pregnancy.

[Placental lactogen level and activity of oxytocinase, beta-glucuronidase and thermostable alkaline phosphatase isoenzyme in blood serum of women with ectopic pregnancy]. / Poziom laktogenu lozyskowego oraz aktywnosc oksytocynazy, beta-glukuronidazy i termostabilnego izoenzymu fosfatazy alkalicznej w surowicy krwi kobiet z ciaza ektopowa.

The lack of literature data dealing with placental lactogen concentration as well as with the other biochemical parameters in blood serum in women with ectopic pregnancy was the reason we turned to that problem. In eight patients with ectopic pregnancy there was determined placental lactogen level and oxytocinase activity as well as the activity of beta-glucuronidase and thermostable alkali phosphatase isoenzyme in blood serum. The results obtained were compared to the concentration of those parameters in blood serum in women with ectopic pregnancy and to those of not pregnant women. It was stated that in women with ectopic pregnancy there was produced placental lactogen and its concentration in blood serum was lower (about 30 percent) than that in women with ectopic pregnancy. Similarly, mean value of oxytocinase activity in women with ectopic pregnancy was twice lower in comparison to that of ectopic pregnancy, while beta-glucuronidase activity was twice higher when compared to that of ectopic pregnancy values. Placental alkali phosphatase isoenzyme activity was similar in both groups of pregnant women.