OBJECTIVE: The trophoblast implantation can determine pregnancy outcome. Our previous results have shown correlation between the events of the trophoblast implantation and the pregnancy outcome. Structural changes in the wall of spiral arteries result low vascular resistance in the uterine arteries in physiological implantation. The adverse pregnancy outcome could be predicted by the absence of decreased uterine vascular resistance in the first trimester measured by color-Doppler ultrasonography. METHODS: Vascular resistance of the uterine arteries was measured in the 10-12th weeks of gestation by color-Doppler ultrasonography. At the same time maternal serum samples were taken and stored at -70 Celsius. The serum progesterone, prolactin, beta-hCG and CRH levels were measured by radio-immune assay. The data of the pregnancy outcome were registered (n=104). ANOVA and Bonferroni tests were used for statistical analysis. RESULTS: The patients were divided into two groups according to the Doppler parameters. The cut off point of the pulsatility indices (PI) was chosen at 2.3. The average PI value was 1.43 +/- 0.51 and 2.59 +/- 0.27 in the groups (mean +/- SEM). The adverse pregnancy outcome was significantly different (p < 0.05) in the two groups; 9 cases in the high vascular resistance group (n = 20) and 3 cases in the low vascular resistance group (n = 84). The serum progesterone and beta-hCG levels were significantly lower in the high vascular resistance group compared to the low resistance one (p < 0.05). The serum prolactin and CRH levels did not show difference between the two groups (p >= 0.05). CONCLUSIONS: The results suggest that the low vascular resistance in the uterine arteries can predict the normal pregnancy outcome (strong negative predictive value). These results are in accordance with elevated levels of known implantation regulating factors such as progesterone and beta-hCG. The failure in this process occurs with high vascular resistance of the uterine arteries and with consequent risk of adverse pregnancy outcome.

Studying proteins expressed in placenta is important to understand its function in pregnancy and fetal growth. Here, we present protein expression profiling from normal human placenta by 2-D gel – MS/MS approach that resulted in identification of 117 unique proteins. Integration with earlier analyses resulted in a profile of 423 non-redundant proteins, 75 of them being new identifications unique to this study including their isoforms. We present a compilation of placental protein expressions identified by proteomic approaches, their functions and known clinical implications. We believe that our dataset would be a useful resource for studies related to placental dysfunction.

To investigate placental protein 13 (PP13) localization in relation to cytoskeleton and lipid rafts in preeclampsia and HELLP syndrome.Placental cryosections from patients with preeclampsia and HELLP, and controls were stained for PP13, actin, PLAP (lipid raft marker), and CD71 (nonraft marker). BeWo cells exposed to stress conditions were stained for PP13 and actin. Protein localizations were investigated by confocal microscopy, PP13 concentrations by ELISA.PP13-actin colocalization was increased in syncytiotrophoblast juxtamembrane regions in term/preterm preeclampsia and HELLP. PP13-CD71 colocalization was decreased and PP13-PLAP proximity was increased in preterm but not term preeclampsia and HELLP. PP13-release from BeWo cells was inhibited by cytoskeleton disruption, and augmented by Ca2+-influx and ischemic stress.The actin cytoskeleton, probably in connection with lipid rafts, controls trophoblastic "nonclassical" PP13 export. PP13 is released from the syncytiotrophoblast in preterm preeclampsia and HELLP, mimicked in BeWo cells by ischemic stress, suggesting PP13 is a placental alarmin.

It was believed for a long time that functional LH/hCG receptors were present only in gonads. Recent studies have demonstrated, however, that these receptors are also present in several nongonadal organs in the human body. Uterus is one of them. Besides two uterine layers, endothelial cells and smooth muscle of blood vessels in the uterus also contain these receptors. In vivo administration of hCG decreased vascular resistance in the human uterus and in vitro treatment increased vasodilatory and decreased vasoconstrictive eicosanoids in the vessels. These findings led us to investigate whether hCG administration to patients with signs of threatened abortion has any beneficial effect. Patients were treated with either magnesium or progesterone and/or hCG. The results showed that the frequency of patients reaching second trimester was higher when hCG was used, which was paralleled by a significant decrease in uterine vascular resistance. Patients who reached term after treatment had decreased incidence of preterm delivery and intrauterine growth retardation. In conclusion, we suggest that uterine vascular LH/hCG receptors play an important role in the peri-implantation period by increasing uterine blood flow through vasodilatation and also perhaps through angiogenesis and trophoblast invasion, resulting in therapeutic benefit.

International Journal of Gynecology & ObstetricsVolume 70, Issue S1 p. A121-A121 Menopause 1 Estrogen treatment of young patients with malignant hematology diseases P. Toth, P. TothSearch for more papers by this authorT. Masszi, T. MassziSearch for more papers by this authorG. Gimes, G. GimesSearch for more papers by this authorF. Paulin, F. PaulinSearch for more papers by this author P. Toth, P. TothSearch for more papers by this authorT. Masszi, T. MassziSearch for more papers by this authorG. Gimes, G. GimesSearch for more papers by this authorF. Paulin, F. PaulinSearch for more papers by this author First published: 09 December 2003 https://doi.org/10.1016/S0020-7292(00)83396-2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume70, IssueS12000Pages A121-A121 RelatedInformation

To characterize the P2X purinoceptor of arteries of human term placenta, a non-innervated organ, actions of ATP, α,β-methylene-ATP and UTP on de-endothelialized chorionic surface artery segments were compared. ATP and α,β-methylene-ATP caused reversible concentration-dependent contractions, but UTP elicited little or no contraction up to 517 μM. Concentration-effect curves to ATP and α,β-methylene-ATP were parallel, and α,β-methylene-ATP, EC50 4.2±1.2 μM, was 28-times as potent as ATP. At a saturating concentration, 103 μM, α,β-methylene-ATP did not desensitize the ATP receptor. Contractions to ATP and α,β-methylene-ATP were antagonized by 300 μM suramin. These findings indicate that P2X purinoceptors are present in placental chorionic surface arteries and that they differ from P2X purinoceptors in arteries of other tissues.

The present study characterized hCG/LH receptors from messenger ribonucleic acid (mRNA) to protein and whether exogenous hCG can bind and regulate the expression of the cyclooxygenase-1 (COX-1) gene in human fetal membranes from term pregnancy. Northern blotting showed that fetal membranes contain 6.0, 4.4, 2.4, and 1.4 kilobases of hCG/LH receptor mRNA transcripts. In situ hybridization revealed that amnion, chorion, and decidua contain receptor transcripts. Western immunoblotting and immunocytochemistry showed that amnion, chorion, and decidua also contain an 80-kDa receptor protein. Ligand blotting demonstrated that the 80-kDa receptor protein in fetal membranes can bind [125I]hCG, and this binding was inhibited by excess unlabeled hCG. Treatment of fetal membranes with highly purified hCG resulted in a dose- and time-dependent increase in immunoreactive COX-1 protein. The response of hCG was seen in all layers of fetal membranes. The treatment with hCG also resulted in an increase in steady state COX-1 mRNA levels. The action of hCG was prevented by cotreatment with H-89, an inhibitor of protein kinase A, but not by calphostin or lavendustin, which inhibit protein kinase C and tyrosine kinase, respectively. In summary, human fetal membranes contain hCG receptor transcripts and receptor protein that can bind hCG and up-regulate the expression of COX-1 gene.

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF alpha), present in amniotic fluid and/or in fetal blood, could potentially regulate cord functions. The present study investigated the possible presence of functional receptors and EGF and TGF alpha themselves in umbilical cord. The reverse transcription-polymerase chain reaction followed by Southern blotting demonstrated that human umbilical cords contain EGF, TGF alpha, and EGF/TGF alpha messenger ribonucleic acid (mRNA) transcripts. In situ hybridization revealed that these mRNA transcripts are present in vascular endothelial cells and smooth muscle, amnion, and myofibroblasts in Wharton's jelly. Western immunoblotting showed that the cords contain a 170-kilodalton EGF/TGF alpha receptor protein. Immunocytochemistry demonstrated that all of the cells that contained mRNA transcripts also contained corresponding proteins. Umbilical amnion contains more EGF, TGF alpha, and their receptors than any other part of the cord. In the cord, the fetal and middle portions contain more than the placental portion or the vessels inside the placental tissue. The cord receptors can bind [125I]EGF, stimulate receptor autophosphorylation, and increase cyclooxygenase-1 and -2 and prostaglandin E2, suggesting that the receptors are functional. In summary, our study demonstrates that human umbilical cord expresses EGF, TGF alpha, and their common receptor genes. The cord EGF/TGF alpha receptors are functional in terms of binding of EGF, activation of receptor autophosphorylation, and increasing the formation of vasoconstrictive eicosanoid. Thus, EGF, TGF alpha, and their receptors could be one of the determinants of human fetal growth and development by autocrine, paracrine, and endocrine actions in umbilical cord.