Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.

The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs’s cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia

Lack of Association between C385A Functional Polymorphism of the Fatty Acid Amide Hydrolase Gene and Polycystic Ovary Syndrome.

The endocannabinoid system contributes to the regulation of appetite, food intake and energy balance. Fatty acid amide hydrolase is responsible for degradating anandamide, a key messenger of the endocannabinoid system. C385A is a common, functionally active genetic polymorphism of the gene encoding fatty acid amide hydrolase and has been associated with overweight and obesity. Our aim was to establish whether single nucleotide polymorphism C385A has an association with polycystic ovary syndrome or its clinical features.A monocentric pilot study was performed on 63 patients with polycystic ovary syndrome and 67 healthy control subjects. Anthropometric parameters and laboratory data were acquired from subjects. The alleles of the polymorphism were detected using polymerase chain reaction and subsequent cleavage by Eco130I (StyI) restriction endonuclease verified by direct DNA sequencing.No difference was found in minor allele frequency between patient and control groups. Those patients, carrying the C385A polymorphism were associated with higher free thyroxine hormone levels. In the control group, carriers of the polymorphism had significantly lower insulin levels.Our data indicate that the C385A polymorphism of the fatty acid amide hydrolase gene is not a genetic susceptibility factor for the development of polycystic ovary syndrome. However, the polymorphism might have a role in influencing the synthesis or metabolism of different hormones including thyroxin and insulin. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Increased circulating heat shock protein 70 levels in pregnant asthmatics

Asthma is one of the most common diseases complicating pregnancy and represents a risk factor for several maternal and perinatal complications. The natural history of asthma is known to change in pregnancy, but very few data are available in the terms of pathomechanism of this change during gestation. Circulating heat shock protein 70 (Hsp70) levels are decreased in healthy pregnancy, which might reflect physiological immunotolerance. The aim of our study was to determine the serum levels of Hsp70 in asthmatic women during gestation. Forty pregnant women with bronchial asthma and 40 healthy pregnant women matched for maternal and gestational age were involved in this case-control study. Serum Hsp70 levels were measured using the ELISA Kit of R&D Systems. Spirometry and oxygen saturation measurements were performed in asthmatic patients. In asthmatic pregnant women, an increase of serum Hsp70 levels was observed compared to healthy pregnant women (median (25–75 percentile): 0.44 ng/ml (0.36–0.53) versus 0.21 ng/ml (0–0.27), p < 0.001). Fetal birth weight of asthmatic mothers was significantly smaller than of healthy controls, but in the normal range (3,230 g (2,690–3,550) versus 3,550 g (3,450–3,775), p < 0.05). A statistically significant negative correlation between maternal age and serum Hsp70 concentrations (Spearman R = −0.48, p = 0.0018) and a significant positive correlation between gestational age and serum Hsp70 levels (Spearman R = 0.83, p < 0.001) were detected in healthy pregnant women. In conclusion, this study proves an elevation of circulating Hsp70 levels during asthmatic pregnancy compared to healthy pregnant women. However, further studies are warranted to determine the role of circulating Hsp70 in the pathogenesis of maternal and perinatal complications of asthma in pregnancy

Genetic variants of the HSD11B1 gene promoter may be protective against polycystic ovary syndrome

The HSD11B1 gene encodes the type 1 isoform of the 11-beta-hydroxysteroid dehydrogenase that is responsible for the regeneration of glucocorticoids from hormonally-inactive metabolites into active forms in a tissue-specific manner. Altered activity of the enzyme, and certain genetic variants of the HSD11B1 gene, has been associated with various metabolic morbidities. In this study, our aim was to systematically test the potential role of the HSD11B1's single nucleotide polymorphisms (SNPs) in polycystic ovary syndrome (PCOS). Nine HSD11B1 SNPs were selected and genotyped using Taqman SNP assays on real-time PCR in a group of PCOS patients (n = 58) and in age-matched healthy controls (n = 64). Genotype-phenotype correlations were determined and haplotype analysis was performed. An in silico prediction for potential transcription factor binding sites was also performed. Of the 5 promoter SNPs, 3 (rs760951; rs4844880; rs3753519) were less frequent in the PCOS group compared to healthy controls. SNPs rs4844880 and rs3753519 were in a complete linkage and the mutant haplotype (AA) was less frequent in the PCOS group. No association between HSD11B1 variants and clinical, pathological findings was observed in patients, but in healthy women the rs4844880 and the AA haplotype were associated with higher levels of homeostasis model assessment of beta cell function. The polymorphic form of the rs4844880 was predicted to bind Pbx-1. Promoter SNPs of the HSD11B1 gene might exert a potential genetic protective role against the development of PCOS, possibly via their beneficial effect on carbohydrate homeostasis due to facilitation of insulin efflux from pancreatic beta-cells