Search

The endocrine disruptors are chemicals with the capacity to influence physiological processes in the organism, most often through hormonal control. They are present in the environment and in the products of daily use. They are often found in food, released from plastic bottles for water, present in cosmetics or fertilizers. Latest research suggests that they can be released from plastics used in the IVF laboratories and can be even present in the manipulation and cultivation media used for isolation and fertilization of gametes and subsequent cultivation of embryos. Permanent and long-term utilization of these substances has adverse effects in human reproductive health, mainly by the means of interfering with synthesis and action mechanisms of reproductive hormones. Moreover, some endocrine disruptors show a range of adverse effects directly on the gametes or embryos cultured in the in vitro conditions. The article provides an overview on bisphenols detected in plastics and media commonly used in the IVF laboratory and considers their possible impact on effectiveness of the IVF methods in a human laboratory.

Maintaining of female fertility is strictly dependent on proper hormonal regulation. Granulosa cells (GCs) are components of ovarian follicles, and they are important in paracrine regulation of the ovary. Preovulatory follicle GCs are responsible for production of estrogens to the ovary microenvironment and lead to the LH surge. Proper functioning of GCs is necessary to ensure appropriate conditions for oocyte development, maturation, ovulation and its release to the oviduct. Long-term in vitro culture of GCs show significant stem-like characteristics. Understanding the molecular processes underlying GCs differentiation towards different cell lineages may reveal other possible stem cell markers. A transcriptomic analysis of short-term primary in vitro cultured GCs, which were isolated from porcine preovulatory follicles was the major focus of the study. The ontological groups herby considered are associated with endodermal and epithelial tissues. Results were and compare to freshly isolated GC cells. 6 the most reduced expression: HSD17B1, DAPL1, NEBL, MAL2, DAB1, ITM2A were chosen for analysis. These genes have been response for processes associated with GCs development and differentiation towards endodermal and epithelial tissues, which make them important for further consideration.

There are multiple possible applications of stem cells in medicine, from cell-based therapies for degenerative and dystrophic conditions, through novel approaches in cancer treatment, to in vitro organ printing. However, there are still several challenges that need to be overcame before stem cells therapies can be successfully introduced worldwide on a large scale. These include sourcing of stem cells, preventing their aberrant progression and ethical concerns regarding their use in animals and humans. Among the multiple stem cell types present in the human organism from the period of embryonic development to adulthood, this review focuses on the three types that gain the most attention in relation to modern research: embryonic stem cells, induced pluripotent stem cells and adult stem cells. There are a number of obstacles that need to be removed before these cells can be widely applied in clinical practice, including the choice of the perfect source of stem cells, full elucidation of the mechanisms of stem cell differentiation and plasticity, and minimization of adverse side effect potential. Nonetheless, the focus of the scientific community on the topic of stem cells remains unhindered, bringing hope that all of the possible concerns will be addressed in the future.

International audience; Cardiovascular and metabolic disorders present major causes of mortality in the ageing population. Polyphenols present in human diets possess cardiometabolic protective properties, however their underlying molecular mechanisms in humans are still not well identified. Even though preclinical and in vitro studies advocate that these bioactives can modulate gene expression, most studies were performed using targeted approaches. With the objective to decipher the molecular mechanisms underlying polyphenols cardiometabolic preventive properties in humans, we performed integrative multi-omic bioinformatic analyses of published studies which reported improvements of cardiometabolic risk factors following polyphenol intake, together with genomic analyses performed using untargeted approach. We identified 5 studies within our criteria and nearly 5000 differentially expressed genes, both mRNAs and miRNAs, in peripheral blood cells. Integrative bioinformatic analyses (e.g. pathway and gene network analyses, identification of transcription factors, correlation of gene expression profiles with those associated with diseases and drug intake) revealed that these genes are involved in the processes such as cell adhesion and mobility, immune system, metabolism, or cell signaling. We also identified 27 miRNAs known to regulate processes such as cell cytoskeleton, chemotaxis, cell signaling, or cell metabolism. Gene expression profiles negatively correlated with expression profiles of cardiovascular disease patients, while a positive correlation was observed with gene expression profiles following intake of drugs against cardiometabolic disorders. These analyses further advocate for health protective effects of these bioactives against age-associated diseases. In conclusion, polyphenols can exert multigenomic modifications in humans and use of untargeted methods coupled with bioinformatic analyses represent the best approach to decipher molecular mechanisms underlying healthy-ageing effects of these bioactives.

The hepatocyte nuclear factor 4 (HNF-4) is a member of the nuclear receptor superfamily and participates in the regulation of several genes involved in diverse metabolic pathways and developmental processes. To date, the functional domains of this nuclear receptor have not been identified, and it is not known whether its transcriptional activity is regulated by a ligand or other signals. In this report, we show that HNF-4 contains two transactivation domains, designated AF-1 and AF-2, which activate transcription in a cell type-independent manner. AF-1 consists of the extreme N-terminal 24 amino acids and functions as a constitutive autonomous activator of transcription. This short transactivator belongs to the class of acidic activators, and it is predicted to adopt an amphipathic alpha-helical structure. In contrast, the AF-2 transactivator is complex, spanning the 128-366 region of HNF-4, and it cannot be further dissected without impairing activity. The 360-366 region of HNF-4 contains a motif that is highly conserved among transcriptionally active nuclear receptors, and it is essential for AF-2 activity, but it is not necessary for dimerization and DNA binding of HNF-4. Thus, HNF-4 deletion mutants lacking the 361-465 region bind efficiently to DNA as homo- and heterodimers and behave as dominant negative mutants. Remarkably, the full transactivation potential of AF-2 is inhibited by the region spanning residues 371-465 (region F). The inhibitory effect of region F on the HNF-4 AF-2 activity is a unique feature among members of the nuclear receptor superfamily, and we propose that it defines a distinct regulatory mechanism of transcriptional activation by HNF-4.

The skin cells of newborn mice were stably transformed in vivo with the aid of electroporation. The plasmid DNA was introduced subcutaneously followed by high-voltage pulses applied to the skin pleat. NEO-resistant colonies were found in primary cell cultures obtained from the treated skin. The experiments show that in vivo electroporation can be used for the introduction of plasmid DNA into skin cells of mouse.

The hepatocyte nuclear factor-4 (HNF-4) contains two transcription activation domains. One domain, activation function-1 (AF-1), consists of the extreme N-terminal 24 amino acids and functions as a constitutive autonomous activator of transcription. This short transactivator belongs to the class of acidic activators, and it is predicted to adopt an amphipathic α-helical structure. Transcriptional analysis of sequential point mutations of the negatively charged residues (Asp and Glu) revealed a stepwise decrease in activity, while mutation of all acidic residues resulted in complete loss of transcriptional activity. Mutations of aromatic and hydrophobic amino acids surrounding the negatively charged residues had a much more profound effect than mutations of acidic amino acids, since even a single mutation of these residues resulted in a dramatic decrease in transactivation, thus demonstrating the importance of hydrophobic residues in AF-1 activity. Like other acidic activators, the AF-1 of HNF-4 binds the transcription factor IIB and the TATA-binding protein directly in vitro. In addition, the cAMP-response-element-binding-protein, a transcriptional adapter involved in the transactivation of a plethora of transcription factors, interacts with the AF-1 of HNF-4 and co-operates in the process of transactivation by HNF-4. The different protein targets of AF-1 suggest that the AF-1 of HNF-4 may be involved in recruiting both general transcription factors and chromatin remodelling proteins during activation of gene expression.