Lysophosphatidic acid induces the crosstalk between the endovascular human trophoblast and endothelial cells in vitro

Spiral artery remodeling at the maternal–fetal interface is crucial for successful pregnancy and requires the interaction between the first trimester trophoblast and the endothelial cells of the maternal vessels. However, the precise mechanism of this dialog has yet to be determined. The current study investigated whether lysophosphatidic acid (LPA) modulates trophoblast–endothelial crosstalk in vitro. HTR-8/SVneo trophoblast cell line (H8) was seeded on top of Geltrex, incubated with LPA or LPA + NS-398 (selective cyclooxygenase-2 inhibitor), LPA + 1400W (selective inducible nitric oxide synthase inhibitor) or LPA + IL-6 neutralizing antibody and assayed for tube formation to model the acquisition of trophoblast endovascular phenotype. The supernatants were collected and used as conditioned media (CM). To test trophoblast–endothelial crosstalk, the endothelial cell line EA.hy926 was incubated with trophoblast CM. The CM from LPA-induced tubulogenesis stimulated endothelial cells migration and did not modify the apoptosis. Soluble factors derived from cyclooxygenase-2 and IL-6 pathways were involved in H8–EA.hy926 interaction under the LPA effect. Moreover, LPA increased the levels of IL-6 mRNA by cyclooxygenase-2 pathway in H8 cells. Collectively, LPA promotes trophoblast–endothelial crosstalk in vitro and induces the release of trophoblast soluble factors that stimulate endothelial cells migration without changes in apoptosis. The evidence presented here provides new insights about an active role of LPA as a lipid mediator regulating vascular remodeling at the maternal–fetal interface.     

Investigation on silent bacterial infections in specimens from pregnant women affected by spontaneous miscarriage

Miscarriage is one of the main complications occurring in pregnancy. The association between adverse pregnancy outcomes and silent bacterial infections has been poorly investigated. Ureaplasma parvum and urealiticum, Mycoplasma genitalium and hominis and Chlamydia trachomatis DNA sequences have been investigated by polymerase chain reaction (PCR) methods in chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from females with spontaneous abortion (SA, n = 100) and females who underwent voluntary interruption of pregnancy (VI, n = 100). U. parvum DNA was detected in 14% and 15% of SA and VI, respectively, with a mean of bacterial DNA load of 1.3 × 10⁻¹ copy/cell in SA and 2.8 × 10 ⁻³ copy/cell in VI; U. urealiticum DNA was detected in 3% and 2% of SA and VI specimens, respectively, with a mean DNA load of 3.3 × 10⁻³ copy/cell in SA and 1.6 × 10⁻³ copy/cell in VI; M. hominis DNA was detected in 5% of SA specimens with a DNA load of 1.3 × 10⁻⁴ copy/cell and in 6% of VI specimens with a DNA load of 1.4 × 10⁻⁴ copy/cell; C. trachomatis DNA was detected in 3% of SA specimens with a DNA load of 1.5 × 10⁻⁴ copy/cell and in 4% of VI specimens with a mean DNA load of 1.4 × 10⁻⁴ copy/cell. In PBMCs from the SA and VI groups, Ureaplasma spp, Mycoplasma spp and C. trachomatis DNAs were detected with a prevalence of 1%–3%. Bacteria were investigated, for the first time, by quantitative real-time PCR (qPCR) in chorionic villi tissues and PBMCs from women affected by SA and VI. These data may help to understand the role and our knowledge of the silent infections in SA.     

Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide-induced hypocampal neuroinflammation in rats

Our study aimed to analyze the effect of ouabain (OUA) administration on lipopolysaccharide (LPS)-induced changes in hippocampus of rats. Oxidative parameters were analyzed in Wistar rats after intraperitoneal injection of OUA (1.8 µg/kg), LPS (200 µg/kg), or OUA plus LPS or saline. To reach our goal, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), in addition to levels of reduced glutathione (GSH), protein carbonyl (PCO) and lipid peroxidation (LPO) were evaluated. We also analyzed the membrane lipid profile and some important lipids for the nervous system, such as phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidic acid and sphingomyelin. The group that received only LPS showed increased oxidative stress, as evidenced by an increase in LPO (about twice), PCO (about three times) levels, and CAT activity (80%). Conversely, administration of LPS decreased GSH levels (55%), and GPx activity (30%), besides a reduction in the amount of PI (60%) and PC (45%). By other side, OUA alone increased the amount of PI (45%), PE (85%), and PC (70%). All harmful effects recorded were attenuated by OUA, suggesting a protective effect against LPS-induced oxidative stress. The relevance of our results extends beyond changes in oxidative parameters induced by LPS, because nanomolar doses of OUA may be useful in neurodegenerative models. Other studies on other cardenolides and substances related issues, as well as the development of new molecules derived from OUA, could also be useful in general oxidative and/or cellular stress, a condition favoring the appearance of neuronal pathologies.     

High‐resolution conodont biostratigraphy from the Darriwilian Stage (Middle Ordovician) of the Argentine Precordillera and biodiversity analyses: a CONOP9 approach

Ordovician conodonts have been extensively documented in the Argentine Precordillera, providing a robust database for a diverse set of palaeontological studies. Despite the numerous studies, the published taxonomy and stratigraphical ranges, data remain contradictory for particular time intervals. Data from a new conodont collection from the Gualcamayo Formation exposed at the Cerro La Chilca section, and new information on the occurrence and ranges of species from the Las Chacritas and Las Aguaditas sections are presented herein. We used a computer‐assisted numerical sequencing program (CONOP9) to construct a composite stratigraphical range chart from data of 57 conodont species in four sections from the Argentine Precordillera. The identified zones of Lenodus variabilis, Yangtzeplacognathus crassus, Eoplacognathus pseudoplanus and Eoplacognathus suecicus allowed us to verify and adjust the biostratigraphical scheme for the Darriwilian of the Central Precordillera. Additionally, species of the genera Histiodella, namely Histiodella sinuosa, Histiodella holodentata, Histiodella kristinae and Histiodella bellburnenisis, enable a reasonable correlation between the Histiodella‐based zonation and the Baltoscandian zonation. Conodont diversity is evaluated using conventional measures (total diversity and normalized diversity) and an interval‐free approach with CONOP9 software. Our data show a positive pattern in conodont diversification, increasing rapidly through the L. variabilis to the Y. crassus zones and reaching a peak in the E. pseudoplanus Zone. When analysing diversity fluctuations with respect to the environmental changes within the depositional basin, migrations in and out of the basin related to local sea level fluctuations appear to be an important process driving the conodont diversity pattern in the Precordillera.