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Background: Inflammation is a condition that jeopardizes the continuity of pregnancy because it increases the secretion of chemokines that favor the migration of leukocytes from maternal and fetal circulations to the cervix, placenta, and the chorioamniotic membranes. During pregnancy, the level of prolactin (PRL) in the amniotic fluid is high; there is evidence to suggest that PRL contributes to maintain a privileged immune environment in the amniotic cavity. We test the effect of prolactin on the secretion profile of chemokines in human fetal membranes.Methods: Nine fetal membranes collected from healthy nonlabouring cesarean deliveries at term. We placed whole membrane explants in a two-chamber culture system. Choriodecidua and amniotic chambers were pretreated with 250, 500, 1000, or 4000 ng/ml of PRL for 24 h, then choriodecidua was cotreated with 500 ng/ml of lipopolysaccharide (LPS) and PRL for 24 h. We used ELISA to measure secreted levels of four chemokines (RANTES, monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and IL-8) in both amnion and choriodecidua regions.Results: In comparison with basal conditions, LPS treatment induced significantly higher secretion of RANTES, MCP-1, and MIP-1α, but not of IL-8. RANTES was mainly produced by choriodecidua and cotreatment with PRL significantly decreased its LPS-induced secretion. MCP-1 was primarily produced by the amnion and its secretion was only inhibited by 4000 ng/ml of PRL. Both membrane regions produced MIP-1α, which was significantly inhibited at 1000 and 4000 ng/ml PRL concentrations. IL-8 showed no significant changes regardless of PRL concentration.Conclusion: PRL inhibits the differential secretion of proinflammatory chemokines by human fetal membranes. [ABSTRACT FROM AUTHOR]

Progesterone is an essential hormone that induces deep immune adaptations favoring pregnancy maintenance. We aimed at evaluating the effects of progesterone on the synthesis of pro- and anti-inflammatory cytokines by mononuclear cells isolated from human placental blood stimulated with lipopolysaccharide, emulating an infection-inflammation environment. Mononuclear cells isolated form human placental blood were obtained from nine women undergoing elective cesarean delivery at term (not in labor), isolated by density gradient sedimentation, cultured and co-stimulated with lipopolysaccharide (500 ng/ml) fromEscherichia coliin the presence or not of progesterone (0.01, 0.1, or 1.0 µM) for 24 h. Culture supernatants were assayed for pro-inflammatory (IL-1β, TNFα, IL-6), anti-inflammatory (IL-10) cytokines, chemokines (IL-8, MIP-1α) and total MMP-9 by ELISA. In comparison with basal conditions, lipopolysaccharide treatment induced IL-1β, TNFα, IL-6, IL-8, MIP-1α, and MMP-9 synthesis. lipopolysaccharide co-treatment with progesterone significantly decreased the bacterial endotoxin-induced IL-1β, TNF-α, IL-6, IL-8, and MIP-1α secretion. In contrast, co-treatment with progesterone increased the level of IL-10 secreted to the culture medium. The present results support the concept that progesterone can modulate––partially––the inflammatory response of professional immune cells isolated from placental blood. Therefore, progesterone might be part of the natural compensatory mechanism that limits the cytotoxic effects associated with an intrauterine infection process during gestation. [ABSTRACT FROM PUBLISHER]

During pregnancy, prolactin (PRL) is a neuro-immuno-cytokine that contributes actively to the crosstalk between the immune and endocrine systems and, thus, to the creation of an immune-privileged milieu. This work aims to analyze the capacity of PRL to modulate the synthesis and secretion of pro-inflammatory markers associated with labor. Studies were conducted using human fetal membranes at term mounted in a model of two independent chambers. The choriodecidual region was stimulated with 500-ng/mL lipopolysaccharide (LPS), and the amnion and choriodecidual region were co-simulated with different concentrations of PRL that can arise during pregnancy: 250, 500, 1000, and 4000ng/mL. Following these co-treatments, the tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 levels were measured in both compartments. As expected, treatment with LPS induced all cytokines to increase. Co-stimulation with the highest tested concentration of PRL induced significant decreases in TNF-α in the choriodecidual region and IL-1β in both regions of the fetal membranes. PRL did not modified the IL-6 and IL-10 secretion profile. These findings, coupled with clinical evidence, suggest that the high level of PRL in the amniotic cavity is involved the mechanism by which the fetal-placental unit regulates the equilibrium between pro- and anti-inflammatory modulators., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background & Aim: Adiponectin and ghrelin are hormones that participate in hepatic lipid metabolism, and their expression in liver tissue could have important implications for nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the hepatic expression of ghrelin, adiponectin, AdipoR, and IL-6 in patients with NAFLD and normal liver., Methods: We studied patients with clinical-pathological diagnosis of NAFLD or a normal liver. Patients were classified according to their diagnosis into three groups: normal liver, nonalcoholic hepatic steatosis, and nonalcoholic steatohepatitis (NASH). Adiponectin, AdipoR1, AdipoR2, IL-6, and ghrelin mRNA levels were assessed in biopsies by reverse transcriptase-polymerase chain reaction., Results: Of the 21 patients, three had a normal liver biopsy, 14 had nonalcoholic steatosis, and four had NASH. Patients with NAFLD exhibited significantly higher HOMA-IR and triglyceride concentration (both P<0.05). There was a nonsignificant trend towards higher ghrelin expression in patients with NASH > nonalcoholic steatosis > normal liver. Patients with NASH had significantly higher mRNA adiponectin levels and lower IL-6 levels than did those with a normal liver (P<0.05). AdipoR expression did not differ significantly between groups., Conclusion: Adiponectin overexpression was observed in patients with NASH. The role of hepatic ghrelin in NAFLD requires further research.

Background and Objective: Iron overload has been associated with HFE mutations (C282Y and H63D). We investigated the association between these mutations and high serum ferritin in a sample of healthy adult men., Design and Methods: We enrolled unrelated blood donors from three hospitals in Mexico City in a crosssectional study. Serum ferritin (SF) was determined to define iron overload, and HFE gene mutations were identified by PCR-RFLP., Results: We evaluated 2524 male blood donors and included 246 individuals for each group. We identified 108 individuals with HFE gene mutation, 20.5 % were heterozygote (wt/H63D or wt/C282Y) and the remaining homozygote (H63D/ H63D). The genotype wt/C282Y was observed in two cases, none cases with C282Y/C282Y. The allelic frequency of H63D and C282Y was 0.115 and 0.002, respectively. We observed different association for H63D allele with iron overload (OR 1.54, CI 95 %1.16-2.03) and none in allele C282Y. Although values averages were different, the extreme dispersion of serum ferritin not showed statistically significant differences between H63D and C282Y alleles and ferritin concentrations., Conclusions: The male unrelated blood donors from Mexico City with iron overload prevalence of 13.8% hold similarities with other populations from Europe o America continent, respecting the allele frequency H63D. Nevertheless, allele frequency C282Y is lower than that observed in descendents from northern Europe. We have not observed statistic difference of SF or iron overload frequency by effect of both alleles.

Objective: Investigate the association between polymorphisms in the leptin receptor gene associated with obesity and gallstone disease., Design: We conducted a cross-sectional study, carried out at a tertiary setting., Subjects: We enrolled 97 subjects, comprising 54 subjects with gallstones (cases) and 43 controls (without gallstones)., Measurements: Diet was assessed using a validated questionnaire for the Mexican population. Body mass index, waist circumference, serum glucose,insulin, leptin, lipids and lipoproteins levels were measured. Insulin resistance was calculated by HOMA-IR. Genomic DNA was isolated from lymphoblastoid cells, and Q223R and K656N polymorphisms in the leptin receptor gene were typed using polymerase chain reaction. Unconditional univariate logistic regression analysis was conducted to estimate the probability of gallstone disease associated with the polymorphisms as main effect., Results: Cases were different in gender(40.74% males in cases vs 74.41% in controls; p < 0.001), older (49.74 vs 44.83 years; p < 0.05), and had more body fat (32.34% vs 28.14%; p = 0.01). Individuals carrying the polymorphism Q223R exhibited a higher BMI (28.44 +/- 6.6 kg/m2 vs 25.94 +/- 3.67 kg/m2, p < 0.05) and waist circumference (96.7 +/- 16.39 cm vs 89.2 +/- 11.05 cm, p < 0.05). In univariate analysis, we did not observe a relation between the presence of a R223 or N656 genotype and gallstone disease in our population (OR = 0.78, 95% CI 0.35-1.73)., Conclusion: Obesity-related leptin receptor polymorphisms are not associated with gallstones disease.

Objective: To characterize the molecular nature of the chemotactic signal for sperm contained in human follicular fluid (FF)., Design: Follicular fluid was fractionated and several procedures were followed to the physicochemical initial characterization of sperm chemotactic compound(s)., Main Outcome Measure: Relative chemotactic activity of each fraction was measured in a double chamber device., Results: Sperm chemotaxis was found to be associated with a lipid-like molecule extracted from FF. Several steroids were assayed individually and only P showed sperm chemotactic properties in dose-response curves., Conclusions: In this paper we present experimental evidence to support the hypothesis that P, the main steroid component of FF, is a mediator of sperm chemoattraction in human beings.

Matrix metallo proteinases (MMP) are the physiological mediators of collagen degradation and its participation in physiopathogenesis of premature rupture of membranes has been suggested by our group. With the idea of defining if some MMP become active active in a coordinated way with labor in fetal membranes, we analyzed enzymatic activity and immunoreactive protein present in extracts of amnion and chorion. It was possible to identify the presence of MMP-9 in extracts of membranes obtained during cesarean sections, without labor, although its activity/quantity was faintly detectable. Instead, extracts of fetal membranes obtained during active labor showed large activity/quantity of this MMP. With a monoclonal antibody, it was possible to show that the active form of MMP-9 could only be found in samples with labor. MMP-9 and its messenger RNA, were localized by immunohistochemistry and in situ hybridization in amniotic epithelium, in some fibroblasts of the compact layer and in trophoblast-like cells in chorion. It is concluded that: 1. Activity and quantity of MMP-9 increase selectively associated to labor; and 2. That this enzyme is expressed by different cellular populations of fetal membranes.