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Objective: This study aimed to describe characteristics of cervicovaginal cytokines obtained during pregnancy from women who subsequently delivered at term., Study Design: We used repeated measures of 20 cervicovaginal cytokines, collected on average on a monthly basis, from the second to the ninth month of gestation among 181 term pregnancies in the Mexico City Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses cohort (2009-2014). Cytokines were quantified using multiplex assay., Results: Cytokine distributions differed more between than within cytokines. Across trimesters, cytokines interleukin (IL)-1Ra, IL-1α, and IL-8 consistently had high concentrations compared with other measured cytokines. Cytokine intraclass correlation coefficients ranged from 0.41 to 0.82. Spearman's correlation coefficients among cytokine pairs varied but correlation directions were stable; 95.3% of the 190 correlation pairs remained either negative or positive across trimesters. Mean longitudinal patterns of log-transformed cytokines from Tobit regression varied across but less within cytokines., Conclusion: Although mean concentrations of cervicovaginal cytokines among term pregnancies were high, they were largely stable over time. The high cytokine concentrations corroborate that pregnancy is associated with an active inflammatory state. These characterizations may serve as a baseline for comparison to other obstetric outcomes, which may be helpful in understanding deviations from normal gestational inflammation., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Determine the dose of Vitamin C able to maintain a leukocyte Vitamin C concentration of > or =18 microg/10(8) cells, in pregnant women with 28 to 32 weeks of gestation, in order to compile a database to estimate the daily recommended intake (DRI) during pregnancy., Methodology: Stage 1: acute supplementation study. A group of 10 healthy women in late first and early second trimester pregnancy were supplemented with 0 to 200 mg vitamin C/day during one week each. Stage 2: a randomized double blind study (placebo vs. vitamin C [100 mg/d]) was carried out with 52 women studied from week 20 to week 32 of pregnancy. Their plasma and leukocyte vitamin C concentrations were measured every 4 weeks to evaluate the previously established supplementation dose., Results: Stage 1: with the 100 mg/day dose, leukocyte vitamin C saturation was reached without increasing urinary excretion. Stage 2: leukocyte concentration of vitamin C decreased throughout pregnancy in women receiving placebo, while supplemented women maintained their concentrations > or =18 microg/10(8) cells., Conclusion: A 100 mg/day dose of vitamin C during the second half of pregnancy keeps leukocyte storage and could be useful to establish the DRI of Vitamin C during pregnancy.

Objective: Human pregnancy disorders such as preeclampsia are thought to involve variations in cytokine levels. It has been proposed that, in preeclamptic women, a balance favoring the Th1-type over the Th2-type cytokine profile determines local or systemic immunologic responses to pregnancy and that this may cause defective placental implantation and placental ischemia, which activate systemic endothelial cells. The purpose of this study was to determine whether cytokine expression differs in the maternal, choriodecidual, and fetal compartments, and between women with or without preeclampsia., Methods: Plasma concentrations of interferon gamma (IFNgamma), interleukin (IL)-2, IL-4, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) in samples obtained from maternal peripheral blood (MPB), choriodecidual (CD), and fetal cord (FC) blood compartments of 17 women with preeclampsia and in 15 normotensive women. Intracellular concentrations of IFNgamma and IL-2 in T lymphocytes were assessed by flow cytometry., Results: Plasma IFNgamma concentrations in both MPB and CD compartments were significantly higher in preeclamptic than in normotensive women. Maternal plasma IL-4 concentration was significantly lower in preeclamptic than in normotensive women. Intracellular IFNgamma and IL-2 concentrations did not differ significantly between preeclamptic and normotensive women., Conclusions: The dominant Th1-type over Th2-type cytokine profile is evident in MPB, but not in the CD and FC blood compartments. This might reflect the complex cytokine networks in the fetal-placental interface and might involve trophoblasts or decidual and endothelial cells, which could account for the increased plasma IFNgamma concentration and T-helper cell number.

The Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses Study (PRINCESA) cohort was set up to evaluate associations between air pollution and birth outcomes among pregnant persons in Mexico City. Specifically, the study was designed to improve air pollution exposure assessment and elucidate biological mechanisms underlying associations between maternal exposures and adverse pregnancy outcomes. Pregnant persons (all women) (N = 935) between ages 18–45 who lived and/or worked in metropolitan Mexico City, Mexico, from 2009 to 2015 and liveborn singleton infants (N = 815) of participants who completed follow-up were enrolled in the cohort. We followed participants monthly from enrollment to delivery and the following categories of data were obtained: demographic, medical and obstetric history, geo-referenced data, repeated measures on daily activity patterns, reported food intake, anthropometric, clinical and obstetric data, 20 serum and 20 cervicovaginal cytokines, and lower reproductive tract infection. Repeated ultrasound measures of fetal parameters and infant birth data are also included in the study's database. In addition, PRINCESA investigators calculated air pollution exposure measures for six pollutants measured by the Mexico City Atmospheric Monitoring System (SIMAT). These estimates utilize participants' addresses to account for spatial variation in exposure (nearest monitor, inverse distance weighting, and kriging) and are available daily during pregnancy for participants. To date, associations between environmental and nutritional impacts on maternal and child health outcomes have been evaluated. PRINCESA has a comprehensive database of maternal and infant data and biological samples and offers collaboration opportunities to study associations between environmental and other factors, including nutrition and pregnancy outcomes. [ABSTRACT FROM AUTHOR]

High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 μm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for "below the median" or "above the median", where the beta estimate is the change in BP at a pollutant's median versus BP at the pollutant's minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP. [ABSTRACT FROM AUTHOR]

Background/objective: Changes in metabolism and extensive hemodynamic adjustments occur during normal pregnancy. The presence of maternal obesity imposes an overload to these physiological adaptations that may result in increased risk for the development of cardiometabolic complications during and after pregnancy. The aim of this study is to describe total cholesterol (TC), triglycerides (TG), glucose, and arterial blood pressure (BP) trajectories and to analyze the association of these cardiometabolic risk indicators during pregnancy with pre-pregnancy body mass index (pBMI) and monthly gestational weight gain (MGWG). Subjects/methods: A prospective cohort study of pregnant women was conducted in Mexico City. Monthly samples of blood were taken during clinical follow-up and biochemical and blood pressure were measured during each visit. Adjusted linear mixed-effect regression models were fit to describe the trajectories of these biomarkers during pregnancy and to analyze the association with pBMI and MGWG. Results: Seven hundred and twenty women were included of which 16.6% had pre-gestational obesity, 33.2% had pre-gestational overweight, 45.8% had normal pBMI and 4.4% had pre-gestational underweight. Women with pre-gestational obesity had higher lipids concentrations in the beginning of pregnancy (TC: β ̂ = 33.08, p = 0.010; TG: β ̂ = 31.29, p = <0.001) but the concentrations increased less than in women with normal pBMI (TC: β ̂ = −14.18, p = 0.001; TG: β ̂ = −5.42, p < 0.001). By the end of pregnancy, women with pre-gestational obesity had lower concentrations of lipids than women with normal pBMI. By contrast, women with pre-gestational obesity had higher glucose concentrations and higher BP levels than women with normal pBMI over pregnancy. Conclusions: pBMI is differentially associated with longitudinal trajectories of maternal biochemical markers of cardiometabolic risk. MGWG did not significantly affect the biochemical indicators or BP trajectories. Our results suggest that pBMI is more relevant to predicting adverse cardiometabolic markers trajectories during pregnancy than MGWG. [ABSTRACT FROM AUTHOR]

Health systems and society are facing the growing problem of obesity and its accompanying comorbidities. New approaches to reduce these problems must be oriented to population groups in which long-lasting effects of interventions may occur. Biological processes occurring during the first 1000 days of life, which may be modulated by environmental modifications and result in phenotypes with differential risk for noncommunicable chronic disease, constitute an opportunity for interventions. The nutritional and general health conditions of pregnant women and the fetus, as well as toddlers, can be improved with interventions during the first 1000 days, offering pregnancy care, promoting breastfeeding, instructing on the use of complementary foods, and educating on the adequacy of the family dietary patterns for children. Evidence that interventions during this period result in promotion of children's growth and development, influencing the risk for development of obesity in infancy, is available. In this article, an ongoing program in Mexico City directed to offer continuum of care during the first 1000 days is described. [ABSTRACT FROM AUTHOR]

Although the isolated effects of several specific nutrients have been examined, little is known about the relationship between overall maternal diet during pregnancy and fetal development and growth. This study evaluates the association between maternal diet and low birthweight (LBW) in 660 pregnant women from the Pregnancy Research on Inflammation, Nutrition,& City Environment: Systematic Analyses (PRINCESA) cohort in Mexico City. Using prior day dietary intake reported at multiple prenatal visits, diet was assessed prospectively using a priori (Maternal Diet Quality Score [MDQS]) and a posteriori (dietary patterns extracted by factor analysis) approaches. The association between maternal diet and LBW was investigated by logistic regression, controlling for confounders. Adherence to recommended guidelines (higher MDQS) was associated with a reduced risk of LBW (OR, 0.22; 95% confidence interval [0.06, 0.75], P <.05, N = 49) compared with the lowest adherence category (reference group), controlling for maternal age, education, height, marital status, pre‐pregnancy body mass index, parity, energy intake, gestational weight gain, and preterm versus term birth; a posteriori dietary patterns were not associated with LBW risk. Higher adherence to MDQS was associated with a lower risk of having an LBW baby in this sample. Our results support the role of advocating a healthy overall diet, versus individual foods or nutrients, in preventing LBW. [ABSTRACT FROM AUTHOR]

Objective: ELABELA is a newly discovered peptide hormone that appears to be implicated in the mechanisms leading to preeclampsia, independently of angiogenic factors. The aim of the current study was to investigate whether women with early- or late-onset preeclampsia have altered ELABELA plasma concentrations compared to gestational-age-matched normal pregnant women.Methods: This retrospective cross-sectional study focused on the maternal plasma samples collected from 232 women with a singleton pregnancy who were allocated into the following groups: (1) early-onset preeclampsia (<34 weeks of gestation, N = 56); (2) late-onset preeclampsia (≥34 weeks of gestation, N = 57); and (3) gestational-age-matched controls with a normal pregnancy [(<34 weeks of gestation, N = 59); (≥34 weeks of gestation, N = 60)]. ELABELA plasma concentrations were determined using a validated enzyme immunoassay.Results: (1) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared with those from gestational-age-matched controls with a normal pregnancy [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 4.17 ng/mL (IQR, 3-11.19 ng/mL), p =.001]; (2) ELABELA plasma concentrations in patients with early-onset preeclampsia do not differ from those of normal pregnant women [median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL) versus median: 4.02 ng/mL (IQR, 3.26-7.49), p = .32]; and (3) ELABELA plasma concentrations are higher in patients with late-onset preeclampsia compared to those with early-onset preeclampsia [median: 7.99 ng/mL (IQR, 5.3-13.95 ng/mL) versus median: 6.09 ng/mL (IQR, 2.8-10.66 ng/mL), p = .01].Conclusion: ELABELA plasma concentrations are higher in patients with late-onset preeclampsia than in those with a normal pregnancy. However, women with early-onset preeclampsia have similar ELABELA plasma concentrations to those with a normal pregnancy. These findings provide insight into the ELABELA axis during the human syndrome of preeclampsia. In addition, these data support the concept that different pathophysiologic mechanisms are implicated in early- and late-onset preeclampsia. [ABSTRACT FROM AUTHOR]

DNA methylation status of RXRα gene promoter has been correlated with maternal diet during early pregnancy, and associated with offspring’s adiposity and bone mineral content. In adult life, increased methylation of RXRα promoter region is associated with myocardium pathologies. Early growth response proteins (EGR) are zinc finger transcription factors associated with several cellular pathways such as inflammation, apoptosis, and cardiopathies. DNA-binding sequences of EGR proteins have been reported in the RXRα gene promoter using chromatin immunoprecipitation methods. Here, we used correlations between the maternal pre-pregnancy body mass index (p-BMI), gestational weight gain (GWG), and birth weight (BW) as indirect indicators of the maternal nutritional status as modifier of DNA methylation in the offspring. DNA methylation status from newborns’ umbilical vein blood in full-term pregnancy was evaluated in a short sequence (116 pb) of the RXRα gene promoter that contains the elements of response sequence for EGR proteins. Fifty-three bisulfite-modified DNA samples were assessed through methyl-sensitive high-resolution melting (MS-HRM) analysis. To validate the results, we directly sequenced MS-HRM samples to confirm the presence of CpG-methylated positions. In addition, the RXRα protein levels in extracts of umbilical vein blood were evaluated by western blot. We found differential methylation in a specific locus of the RXRα promoter surrounding the EGR-binding sequence; however, no correlation was found with the level of RXRα protein expression. Variability in the methylation status of the RXRα promoter near the EGR transcription factor binding site in newborn cord blood provides controversial epigenetic insights into RXRα regulation via EGR proteins. [ABSTRACT FROM AUTHOR]

Abstract: Neonatal CD71+ erythroid cells are thought to have immunosuppressive functions. Recently, we demonstrated that CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm labor (PTL) are reduced to levels similar to those of term neonates; yet, their functional properties are unknown. Herein, we investigated the functionality of CD71+ erythroid cells from neonates born to women who underwent spontaneous preterm or term labor. CD71+ erythroid cells from neonates born to women who underwent PTL displayed a similar mRNA profile to that of those from term neonates. The direct contact between preterm or term neonatal CD71+ erythroid cells and maternal mononuclear immune cells, but not soluble products from these cells, induced the release of proinflammatory cytokines and a reduction in the release of TGF‐β. Moreover, PTL‐derived neonatal CD71+ erythroid cells (1) modestly altered CD8+ T cell activation; (2) inhibited conventional CD4+ and CD8+ T‐cell expansion; (3) suppressed the expansion of CD8+ regulatory T cells; (4) regulated cytokine responses mounted by myeloid cells in the presence of a microbial product; and (5) indirectly modulated T‐cell cytokine responses. In conclusion, neonatal CD71+ erythroid cells regulate neonatal T‐cell and myeloid responses and their direct contact with maternal mononuclear cells induces a proinflammatory response. These findings provide insight into the biology of neonatal CD71+ erythroid cells during the physiologic and pathologic processes of labor. [ABSTRACT FROM AUTHOR]

Problem Activated/effector T cells seem to play a role in the pathological inflammation associated with preterm labor. The aim of this study was to determine whether in vivo T-cell activation by a monoclonal α CD3ε antibody induces preterm labor and birth. Method of study Pregnant B6 mice were intraperitoneally injected with a monoclonal α CD3ε antibody or its isotype control. The gestational age, the rates of preterm birth and pup mortality at birth as well as the fetal heart rate and umbilical artery pulsatility index were determined. Results Injection of a monoclonal α CD3ε antibody led to preterm labor/birth (α CD3ε 83 ± 16.97% [10/12] vs isotype 0% [0/8]) and increased the rate of pup mortality at birth (α CD3ε 87.30 ± 8.95% [77/85] vs isotype 4.91 ± 4.34% [3/59]). In addition, injection of a monoclonal α CD3ε antibody decreased the fetal heart rate and increased the umbilical artery pulsatility index when compared to the isotype control. Conclusion In vivo T-cell activation by a monoclonal α CD3ε antibody in late gestation induces preterm labor and birth. [ABSTRACT FROM AUTHOR]

Abstract: Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. [Copyright &y& Elsevier]

Problem Spontaneous labor at term involves leukocyte recruitment and infiltration into the choriodecidua; yet, characterization of these leukocytes and their immunological mediators is incomplete. The purpose of this study was to characterize the immunophenotype of choriodecidual leukocytes as well as the expression of inflammatory mediators in human spontaneous parturition at term. Method of study Choriodecidual leukocytes were analyzed by FACS, immunohistochemistry, and RT- PCR in three different groups: (i) preterm gestation delivered for medical indications without labor; (ii) term pregnancy without labor; and (iii) term pregnancy after spontaneous labor. Results Two T-cell subsets of memory-like T cells ( CD3+ CD4+ CD45 RO+ and CD3+ CD4− CD8− CD45 RO+ cells) were identified in the choriodecidua of women who had spontaneous labor. Evidence for an extensive immune signaling network composed of chemokines ( CXCL8 and CXCL10), chemokine receptors ( CXCR1-3), cytokines ( IL-1β and TNF-α), cell adhesion molecules, and MMP-9 was identified in these cells during spontaneous labor at term. Conclusions The influx of memory-like T cells in the choriodecidua and the evidence that they are active by producing chemokines and cytokines, and expressing chemokine receptors, cell adhesion molecules, and a matrix-degrading enzyme provides support for the participation of the adaptive immune system in the mechanisms of spontaneous parturition at term. [ABSTRACT FROM AUTHOR]

Objective: To determine whether vitamins C and E supplementation lowers oxidative stress marker levels and improves pregnancy rate in women with endometriosis.Methods: Thirty-four women with endometriosis received a bar containing vitamins C and E (343 mg and 84 mg, respectively) or placebo for 6 months. Plasma and peritoneal fluid levels of malondialdehyde (MDA) and lipid hydroperoxides (LOOHs) were measured for all women and compared between the 2 groups. Data were analyzed by the t test or 1-way analysis of variance for parametric data and the Mann-Whitney rank sum test or Kruskall-Wallis test for nonparametric data. The Fisher exact test was used to compare pregnancy rates.Results: After 4 months, the study group had lower levels of MDA and LOOHs than the control group, and the difference became statistically significant in the fourth month for MDA levels and in the sixth month for LOOH levels. The postintervention pregnancy rates were 19% and 12% in the supplementation and placebo groups, respectively, but the difference was not significant.Conclusions: Vitamins C and E supplementation was associated with a decrease in the concentration of oxidative stress markers in women with endometriosis. The pregnancy rate, however, did not improve during or after the intervention. [ABSTRACT FROM AUTHOR]

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ginecología y Obstetricia de México is the property of Federacion Mexicana de Ginecologia y Obstetricia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Vitamin C is involved in the synthesis and degradation of collagen and is important for maintenance of the chorioamniotic membranes. Inadequate availability of ascorbic acid during pregnancy has been proposed as a risk factor for premature rupture of the chorioamniotic membranes (PROM). Objective: The objective of the study was to evaluate the effective-ness of 100 mg vitamin C/d in preventing PROM. Design: A controlled double-blind trial was performed. Pregnant women (n = 126) in their 20th wk of gestation were invited; 120 accepted and were randomly assigned to 2 groups (100 mg vitamin C/d or placebo). Every 4 wk, plasma and leukocyte vitamin C concentrations were measured, and each subject was evaluated for cer-vicovaginal infection. The incidence of PROM was recorded for each group as an indicator of the protective effect of vitamin C supplementation. Results: One hundred nine patients finished the study. Mean plasma vitamin C concentrations decreased significantly throughout the pregnancy in both groups (P = 0.001), and there were no significant differences between groups. Between weeks 20 and 36, mean leukocyte vitamin C concentrations decreased from 17.5 to 15.23 μg/ 108 cells in the placebo group and increased from 17.26 to 22.17 μg/108 cells in the supplemented group (within- and between-group differences: P = 0.001). The incidence of PROM was 14 per 57 pregnancies (24.5%) in the placebo group and 4 per 52 pregnancies (7.69%) in the supplemented group (relative risk: 0.26; 95% CI: 0.078, 0.837). Conclusion: Daily supplementation with 100 mg vitamin C after 20 wk of gestation effectively lessens the incidence of PROM. [ABSTRACT FROM AUTHOR]

Extracellular matrix homeostasis is a key process in the maintenance of the tensile strength of the amniochorion. This tensile strength guarantees the role of the membranes as a physical and functional boundary for the fetus during human pregnancy. Pathological rupture of these structures before 37 completed weeks of gestation is known as preterm prelabour rupture of the membranes (PPROM) and it is a major cause of spontaneous preterm labour and preterm birth. A mechanism involving the activation of matrix metalloproteinases (MMP)-9, a 92-kDa type IV collagenase, as an essential mediator of tissue damage is under investigation. The proposed mechanism involves the abnormal expression and activity of MMP-9 with subsequent connective tissue degradation taking place at a time that does not synchronise with other events of labour. The local physiological signal by amniochorion cells to induce MMP-9 expression is not known, but bacterial products and/or the proinflammatory cytokines, IL-1β and TNF-α, as paracrine or autocrine signals may trigger these processes in pregnancies complicated with intra-amniotic infection. These signalling pathways indicate complex cooperative and bidirectional communications between amnion and choriodecidua in response to bacterial products, which include intermembranous cytokine traffic and signalling between tissues. Products secreted in culture by amniochorion and choriodecidual leucocytes, obtained from women who delivered following normal labour in the absence of infection, condition a specific microenvironment that induces collagen degradation in fetal membranes. Further characterisation of the role of choriodecidual leucocytes in the control of extracellular matrix degradation in amniochorion is currently under way. [ABSTRACT FROM AUTHOR]

Objective: Trophoblast differentiation is a critical process for successful implantation and establishment of the human placenta. The aim of this study was to characterize the effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) on the expression of markers of trophoblast function and differentiation.Study Design: Human cytotrophoblasts were stimulated with 1 and 10 ng/mL recombinant TNF-alpha or IL-6. Cell viability was determined and conditioned culture media was analyzed by gelatin zymography to assess protease secretion and by enzyme-linked immunosorbent assays to measure production of beta-human chorionic gonadotropin and oncofetal fibronectin.Results: TNF-alpha increased secretion of urokinase-type plasminogen activator up to 3-fold of basal unstimulated production. Stimulation of cytotrophoblasts with this cytokine also inhibited beta-human chorionic gonadotropin secretion up to 75%. TNF-alpha did not modify the secretion of matrix metalloproteinase-9 and oncofetal fibronectin. IL-6 had no effect on these trophoblast differentiation markers.Conclusion: These results show that TNF-alpha stimulated cytotrophoblasts modulate the expression of differentiation markers, down-regulating the autocrine signals that promote syncytialization, and increasing their invasive capacity through up-regulation of proteases. We suggest that this regulatory mechanism of trophoblast function could play an important role during trophoblast implantation, in pregnancy failure and in the normal and pathologic rupture of fetal membranes. [ABSTRACT FROM AUTHOR]

Objective: To test the effect of prolactin (PRL) on expression of proinflammatory cytokines and matrix metallopeptidase 9 (MMP-9) in vitro. Study Design: Tissue explants were incubated from 4 to 48 hours alone or in the presence of 500 ng/mL PRL, and mRNA expression in tissues and secretion of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), MMP-2, and MMP-9 was quantified. Results: Fetal membranes secreted IL-1β, TNF-α, and MMP-9 in culture with consistent low concentration during the first 24 hours and then increased progressively. The presence of PRL during explant incubation significantly decreased the patterns of IL-1β, TNF-α and MMP-9 secretion along culture (P < .001). MMP-2 secretion was unaffected by PRL. The relative basal expression of IL-1β mRNA (1.2 ± 0.87) was reduced by 80% in the presence of PRL after 32 hours of incubation of the membranes (P = .001). The expression of the TNF-α mRNA was not modified by the presence of PRL (0.06 ± 0.01) compared with the basal expression levels (0.05 ± 0.01). MMP-9 mRNA basal expression (0.018 ± 0.008) was significantly reduced (P = .001) in the presence of PRL after 32 hours (0.002 ± 0.0005). Conclusion: PRL may be a potential candidate as a key signal controlling the expression of signals related to the proinflammatory reaction associated with human labor. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the secretions of zymogen and active forms of matrix metalloproteinase (MMP)-9 and MMP-2 and their specific inhibitors, TIMP-1 and TIMP-2 by fetal membranes stimulated with group B Streptoccocci (GBS). Methods: We used an in vitro experimental model that allowed us to estimate the individual contribution of the amnion (AM) and the choriodecidua (CHD) to the microbial insult. Membranes were obtained after delivery by elective cesarean delivery from women at 37 to 40 weeks of gestation without evidence of either active labor or intrauterine infection. Membranes were mounted in Transwell devices (Costar, New York, NY), physically separating the upper and lower chambers; 1 × 106 CFU of GBS was added to either AM or CHD and the secretions and gelatinolytic activity of MMP-2 and MMP-9 were measured in both compartments by enzyme-linked immunosorbent assay (ELISA) and zymography. TIMPs secretion was measured by ELISA. Both MMPs were immunolocalized in tissue sections. Results: The simultaneous stimulation at both sides was followed by increases of proMMP-9 (85.0 ± 18.63 pg/mL) and proMMP-2 (4.10 ± 1.90 ng/mL) in the CHD (P <.05). When only one side of the membrane was stimulated, the secretion level of proMMP-2 increased 2.3-fold and that of proMMP-9 2.5-fold in the CHD. The active forms of both enzymes did not change with any modality of stimulation. The secretion level of both TIMPs remained without significant changes. CHD and AM were positive for immunoreactive MMP-2 and MMP-9. Conclusion: We propose that infection of fetal membranes with GBS is followed by active secretion of MMP and the CHD is the principal source of these mediators of extracellular matrix degradation. [Copyright &y& Elsevier]