Oxidative Stress-Related Signaling Pathways Predict Oocytes’ Fertilization In Vitro and Embryo Quality

Oocyte development and fertilization are largely influenced by the microenvironment of the follicular fluid (FF), and the exploration of its molecular/metabolic composition may help in improving in vitro fertilization (IVF) outcomes. Here, the concentrations of molecules related to oxidative stress/inflammation were measured in FF from follicles at oocyte retrieval during IVF. Here, the FF antioxidant potential was correlated with the number of retrieved/mature oocytes and the number of fertilized ones. FF collected from the follicles of normal fertilized oocytes presented an elevated antioxidant capability, lower levels of pro-inflammatory molecules (i.e., IL-6, IL-8, IL-12, TGF-beta, and HIF-1 alpha), and a higher IL-10 concentration. FF samples from follicles at oocyte retrieval that resulted in top-quality embryos displayed a peculiar antioxidant capability and a further decrease in proinflammatory molecules when compared with FF, giving rise to poor-quality embryos. Finally, pro-inflammatory molecules were lower and accompanied by a high antioxidant capability in samples giving rise to successful embryo implantation. The antioxidant capability and IL-10 displayed a good predictive ability for fertilization and embryo quality. Overall, our data showed the great influence of oxidative stress on the oocytes' fertilization, and shed light on the importance of controlling the inflammatory and oxidative status of FF to obtain good-quality embryos with significant implantation potential

Selection of young ewe lambs according to their antral follicular count: response to exogenous hormonal stimulation and fertility at first breeding season

Anti-Mullerian Hormone (AMH), Antral Follicular Count (AFC) and the response to exogenous hormonal stimulation have been used, in adults, as suitable markers to determine the ovarian reserve (1-4), to predict oocyte quality (5,6) and a wide variety of fertility indices (6-9). This investigation aims to evaluate if animals selected according to their High or Low AFC at an early prepubertal age show different responses, in the number of follicles and AMH plasma levels, to exogenous hormonal stimulation; to verify whether differences are maintained over time until puberty; and to observe possible variations on fertility at first breeding season

HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

BAckground:HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs). RESULTS: MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPAR\u3b3 activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. CONCLUSIONS: The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients

Molecular Research on Polycystic Ovary Syndrome (PCOS)

: Polycystic ovary syndrome (PCOS) is an endocrine systemic disorder with a prevalence of between 5% and 20% that commonly affects childbearing-aged women [...]

Biocompatibility of Subperiosteal Dental Implants: Effects of Differently Treated Titanium Surfaces on the Expression of ECM-Related Genes in Gingival Fibroblasts

Introduction: Titanium alloys currently are the most used material for the manufacture of dental endosseous implants. However, in partially or totally edentulous patients, varying degrees of maxillary bone resorption usually occur, making the application of these devices difficult or even impossible. In these cases, a suitable alternative is offered by subperiosteal implants, whose use is undergoing a revival of interest following the introduction of novel, computer-assisted manufacturing techniques. Several procedures have been developed for the modification of titanium surfaces so to improve their biocompatibility and integration with bone. Information is, however, still incomplete as far as the most convenient surface modifications to apply with subperiosteal implants, in which an integration with soft mucosal tissues is just as important. Objectives: The present study aimed at evaluating whether different treatments of titanium surfaces can produce different effects on the viability, attachment, and differentiation of gingival fibroblasts, i.e., the cell type mainly involved in osteointegration as well as the healing of soft tissues injured by surgical procedures, in order to verify whether any of the treatments are preferable under these respects. Methodology: The human immortalized gingival fibroblast (CRL-4061 line) were cultured in the presence of titanium specimens previously treated with five different procedures for surface modification: (i) raw machined (Ti-1); (ii) electropolished (Ti-2); (iii) sand-blasted acid-etched (Ti-3); (iv) Al Ti Color (TM) proprietary procedure (Ti-4); and (v) anodized (Ti-5). At different times of incubation, viability and proliferation of cells, was determined along with the changes in the expression patterns of ECM-related genes involved in fibroblast attachment and differentiation: vinculin, fibronectin, collagen type I-alpha 1 chain, focal adhesion kinase, integrin beta-1, and N-cadherin. Three different experiments were carried out for each experimental point. The release from fibroblasts of endothelin-1 was also analyzed as a marker of inflammatory response. The proliferation and migration of fibroblasts were evaluated by scratch tests. Results: None of the five types of titanium surface tested significantly affected the fibroblasts' viability and proliferation. The release of endothelin-1 was also not significantly affected by any of the specimens. On the other hand, all titanium specimens significantly stimulated the expression of ECM-related genes at varying degrees. The proliferation and migration abilities of fibroblasts were also significantly stimulated by all types of titanium surface, with a higher-to-lower efficiency in the order: Ti-3 > Ti-4 > Ti-5 > Ti-2 > Ti-1, thus identifying sandblasting acid-etching as the most convenient treatment. Conclusions: Our observations suggest that the titanium alloys used for manufacturing subperiosteal dental implants do not produce cytotoxic or proinflammatory effects on gingival fibroblasts, and that sandblasting acid-etching may be the surface treatment of choice as to stimulate the differentiation of gingival fibroblasts in the direction of attachment and migration, i.e., the features allegedly associated with a more efficient implant osteointegration, wound healing, and connective tissue seal formation