Objective To test binding affinities for, and inhibitory effects on, myometrium of some oxytocin and vasopressin antagonists with respect to their therapeutic potential.Design Receptor binding studies on transfected cell lines. In vifro contractility studies of human myometrium.Setting The Research Laboratory of Sanofi Recherche, Centre de Toulouse, France and the Departments of Obstetrics and Gynecology, Lund University Hospital, Sweden and Bialystok University Hospital, Poland.Participants Nine women delivered by caesarean section preterm and 37 delivered at term for routine obstetric indications. Results Oxytocin had a high affinity for the oxytocin receptor (K, in mean = 6.8 nmoYL) and bound, to some extent, to the vasopressin V,, receptor (K, = 34.9 nmol/L). Vasopressin displayed higher affinities for vasopressin V,,, V,, and V2 receptors (Ki = 1.4,0-8 and 4.2 nmovL, respectively) than for the oxytocin receptor (Ki = 48 nmoliL). Atosiban and SR 49059 both had a high affinity for the vasopressin V,, receptor (Ki = 4.7 and 7.2 nmoVL, respectively, and a moderate one for the oxytocin receptor (Ki = 397 and 340 nmoVL, respectively). SR 121463 exerted a predominant binding to the V, receptor (K, = 3-0 nmoVL). In the concentration-response experiments levels of up to 10 nmol/L of SR 49059 had no influence on the effect of oxytocin on myometrium from women preterm and at term pregnancy. However, a concentration-dependent inhibition of the responses of both these type of tissues to vasopressin was seen. The effects of EC,o concentrations of oxytocin and vasopressin on term pregnant myometrium were markedly inhibited by 10 nmovL and higher concentrations of SR 49059, the inhibition of the response to vasopressin being more pronounced than that of the oxytocin response. SR 121463 at maximal concentration only caused slight inhibitions of the oxytocin and vasopressin responses. InterventionsConclusions Atosiban and SR 49059 both have moderate binding affinities for the human oxytocin receptor and high binding affinities for the vasopressin V,, one. We demonstrated that SR 49059 inhibits the response of term myometrium to oxytocin and that of both preterm and term myometrium to vasopressin. These observations suggest a therapeutic potential of SR 49059 in preterm labour. The vasopressin V, receptor is apparently not involved to any significant degree in the activation of the pregnant human uterus.

Objective To profile maternal plasma metabolome in spontaneous preterm birth. Method In this retrospective case-control study, we have examined plasma of patient with preterm birth (between 22 and 36 weeks of pregnancy (n = 57)), with threatened preterm labor (between 23 and 36 weeks of pregnancy (n = 49)), and with term delivery (n = 25). Plasma samples were analysed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) in positive and negative polarity modes. Results We found 168 differentially expressed metabolites that were significantly distinct between study groups. We determined 51 metabolites using publicly available databases that could be subdivided into one of the five groups: amino acids, fatty acids, lipids, hormones, and bile acids. PLS-DA models, verified by SVM classification accuracy, differentiated preterm birth and term delivery groups. Conclusions Maternal plasma metabolites are different between term and preterm parturitions. Part of them may be related with preterm labor, while others may be affected by gestational age or the beginning of labor. Metabolite profile can classify preterm or term delivery groups raising the potential of metabolome as a biomarker to identify high-risk pregnancies. Metabolomic studies are also a tool to detect individual compounds that may be further tested in targeted researches.

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Introduction. Nowadays it is thought that the main cause of premature birth is subclinical infection. However, none of the currently used methods provide effective prevention to preterm labor. The aim of the study was to determine the concentration of selected chemokines in sera of patients with premature birth without clinical signs of infection (n = 62), threatened preterm labor (n = 47), and term births (n = 28). Method. To assess the concentration of chemokines in the blood serum, we used a multiplex method, which allows the simultaneous determination of 40 chemokines per sample. The sets consist of the following chemokines: 6Ckine/CCL21, Axl, BTC, CCL28, CTACK/CCL27, CXCL16, ENA-78/CXCL5, Eotaxin-3/CCL26, GCP-2/CXC, GRO (GROα/CXCL1, GROβ/CXCL2 and GROγ/CXCL3), HCC-1/CCL14, HCC-4/CCL16, IL-9, IL-17F, IL18-BPa, IL-28A, IL-29, IL-31, IP-10/CXCL10, I-TAC/CXCL11, LIF, LIGHT/TNFSF14, Lymphotactin/XCL1, MCP-2/CCL8, MCP-3/CCL7, MCP-4/CCL13, MDC/CCL22, MIF, MIP-3α/CCL20, MIP-3-β/CCL19, MPIF-1/CCL23, NAP-2/CXCL7, MSPα, OPN, PARC/CCL18, PF4, SDF-1/CXCL12, TARC/CCL17, TECK/CCL25, and TSLP. Results. We showed possible implication of 4 chemokines, that is, HCC-4, I-TAC, MIP-3α, and TARC in women with symptoms of preterm delivery. Conclusion. On the basis of our findings, it seems that the chemokines may play role in the pathogenesis of preterm labor. Defining their potential as biochemical markers of preterm birth requires further investigation on larger group of patients.

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