Do the levels of tumor makers or proinflammatory cytokines in mid-trimester cervical fluid predict early-stage cervical shortening?

AIM: In the present study, we aimed to assess the biomarkers in mid-trimester cervical fluid that can predict early stage cervical shortening. MATERIAL AND METHODS: We obtained cervical swab specimens from 96 gravidas, after which the cervical length was measured, at approximately 20 weeks of gestation. Cervical length was measured again at 4 weeks after the initial examination. Cervical shortening was noted in 20 women between 20 and 24 weeks of gestation (group A), whereas no cervical shortening was noted in 76 women (group B). We evaluated the use of the levels of tumor markers, proinflammatory cytokines, and matrix metalloproteinase-8 (MMP-8) as candidate biomarkers. CA-125 and carcinoembryonic antigen levels were determined by using an automatic immunoassay system in both groups. Furthermore, IL-1ß, IL-8, tumor necrosis factor-α, and MMP-8 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The levels of inflammatory cytokines and MMP-8 did not differ between the two groups, and were not correlated with cervical length or the change in cervical length. Although CA-125 and carcinoembryonic antigen levels were higher in group A, they were not statistically significant (P = 0.304 and 0.092, respectively). CONCLUSION: Early stage cervical shortening in mid-trimester was not associated with an increase in the levels of tumor markers or proinflammatory cytokines in cervical fluid.

Differential expression of the metastasis suppressor KAI1 in decidual cells and trophoblast giant cells at the feto-maternal interface.

Invasion of trophoblasts into maternal uterine tissue is essential for establishing mature feto-maternal circulation. The trophoblast invasion associated with placentation is similar to tumor invasion. In this study, we investigated the role of KAI1, an antimetastasis factor, at the maternal-fetal interface during placentation. Mouse embryos were obtained from gestational days 5.5 (E5.5) to E13.5. Immunohistochemical analysis revealed that KAI1 was expressed on decidual cells around the track made when a fertilized ovum invaded the endometrium, at days E5.5 and E7.5, and on trophoblast giant cells, along the central maternal artery of the placenta at E9.5. KAI1 in trophoblast giant cells was increased at E11.5, and then decreased at E13.5. Furthermore, KAI1 was upregulated during the forskolin-mediated trophoblastic differentiation of BeWo cells. Collectively, these results indicate that KAI1 is differentially expressed in decidual cells and trophoblasts at the maternal-fetal interface, suggesting that KAI1 prevents trophoblast invasion during placentation.

Amino-terminal pro-brain natriuretic peptide levels in hypertensive disorders complicating pregnancy.

OBJECTIVE: Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is synthesized in cardiac ventricles in response to volume expansion. This study evaluated NT-proBNP levels to determine the clinical correlation with the severity of hypertensive disorders complicating pregnancy. METHODS: NT-proBNP levels of 95 pregnant women (severe preeclampsia [n = 26], mild preeclampsia [n = 15], gestational hypertension [n = 9], and healthy controls [n = 45]) were determined using an electrochemiluminescence immunoassay. RESULTS: Comparisons of the mean values of NT-proBNP levels in the different groups were significantly different, as follows: 1766.43 ± 4197.39 pg/mL (median, 339.8 pg/mL) in severe preeclampsia, 214.97 ± 226.35 pg/mL (median, 152.3 pg/mL) in mild preeclampsia, 39.75 ± 24.85 pg/mL (median, 34.09 pg/mL) in gestational hypertension, and 78.78 ± 81.56 pg/mL (median, 48.54 pg/mL) in the healthy controls. The NT-proBNP levels of the patients with mild and severe preeclampsia were significantly higher than in the patients with gestational hypertension and the healthy control patients. There was no significant difference in NT-proBNP levels between patients with mild and severe preeclampsia (p = 0.17). CONCLUSION: In patients with mild and severe preeclampsia, NT-proBNP levels were elevated. This may reflect ventricular stress and/or subclinical cardiac dysfunction associated with preeclampsia.

Umbilical cord blood amino-terminal pro-brain natriuretic peptide levels according to the mode of delivery.

PURPOSE: To evaluate cord blood amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels according to the mode of delivery. METHOD: Between 1 March and 31 May 2007, 106 blood samples were drawn from the umbilical vein at the time of delivery. Eighty-four NT-proBNP levels [63 term (34 cesarean sections and 29 vaginal deliveries) and 21 preterm births] were analyzed with respect to gestational age, birth weight, Apgar score, newborn gender, and cord blood pH. RESULTS: There was no statistical significance on comparison of the mean NT-proBNP values between the cesarean and vaginal delivery groups (801.9+/-537.7 vs. 724.3+/-542.4 pg/ml, respectively; P=0.572). The correlation of NT-proBNP with gestational age, birth weight, and cord blood pH was -0.616, -0.585, and -0.202, respectively. The mean values for NT-proBNP levels were compared according to the newborn gender (male vs. female; P=0.926), and Apgar score at 1 min [>6 (N=71) vs.

The modulating effects of the overexpression of uncoupling protein 2 on the formation of reactive oxygen species in vascular cells.

Uncoupling protein 2 (UCP-2) is a newly identified member of the mitochondrial anion carrier family and shares 60% sequence identity with the well-characterized thermogenic UCP-1 from brown adipose tissue. Several lines of evidence suggest that UCP-2 is involved in the control of reactive oxygen species (ROS) production by mitochondria. More recently, a direct role for UCP-2 in the regulation of atherogenesis has been suggested by the observation that bone marrow transplantation from UCP-2-deficient mice to low-density lipoprotein receptor-deficient mice markedly increased atherosclerotic lesion size. This review introduces the possible role of UCP-2 in the regulation of atherogenesis in vascular cells. Although the relative contribution of the individual ROS generating systems in the vasculature is still ambiguous, both cell membrane NAD(P)H oxidase and the mitochondrial electron-transport chain have been proposed to play significant roles in the overproduction of ROS. UCP-2 can possibly modify atherosclerotic processes initiated in vascular cells and agents that increase UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes or hypertension.

Differential expression of the PEA3 subfamily of ETS transcription factors in the mouse ovary and peri-implantation uterus.

The objective of the present investigation was to examine the spatio-temporal expression of three members of the ETS family of transcription factors, ERM, ER81, and PEA3, in the peri-implantation mouse uterus and in the ovary. These three factors belong to the PEA3 subfamily and are known to mediate diverse functions ranging from neuronal development to tumor progression. As transcription factors, they regulate the expression of a number of genes with various biological functions. Since several genes with known roles in the reproductive processes have been shown to be under the regulation of one of these factors, we sought to investigate the expression of ERM, ER81, and PEA3 in the mouse ovary and uterus. Quantitative RT-PCR analyses showed that ERM, ER81, and PEA3 were all expressed in the peri-implantation mouse uterus, with higher levels of expression on days 4 and 5 of pregnancy. To determine the cell type-specific expression of these factors, we employed in situ hybridization, the results of which revealed that ERM was expressed in both the epithelium and the stroma on days 4 and 5 of pregnancy. Uterine glands showed a high expression of ERM on those days. ERM was also highly expressed in the corpora lutea of the mouse ovary. Both ER81 and PEA3 were expressed at low levels in the stroma on days 4 and 5. On day 8, while ERM and PEA3 were mainly expressed in the embryo and were at low levels in the maternal decidua in a diffused pattern, ER81 was highly expressed in the vascular bed of the mesometrial deciduum. Both ER81 and PEA3 were undetectable in the mouse ovary. Collectively, these data show that ERM is implicated in the early event of implantation as well as in ovarian functions, while ER81 is involved in the establishment of the maternal vasculature for subsequent placental development. PEA3 is apparently an embryonic factor for early embryogenesis.

Brief exposure to ethanol augments vascular contractility in human chorionic plate arteries.

Heavy alcohol consumption has been known as a risk factor for hypertension, although the mechanism by which alcohol intake causes hypertension remains elusive. We tested the hypothesis that brief exposure to ethanol augments vascular contractility through the stress response in human chorionic plate arteries. Human chorionic plate arteries were mounted in organ baths and exposed to 5% ethanol for 15, 30 or 45 min. Brief exposure for 45 min, but not 15 min, not only augmented contractility to KCl and 5-hydroxytryptamine 5 h after the end of exposure, but also increased the expression of heat shock protein (HSP) 70 in the tissues. Reverse transcription-polymerase chain reaction showed gradual increases of hsp70 mRNA expression, but not heat shock cognate 70 (hsc70), hsp90alpha or glucose regulatory protein 78 (grp78) mRNA expression, in an exposure time-dependent manner 3 h after the end of exposure. These results indicate that ethanol augments vascular contractility through the stress response.