A Bayesian view of murine seminal cytokine networks

It has long been established that active agents in seminal fluid are key to initiating and coordinating mating-induced immunomodulation. This is in part governed by the actions of a network of cytokine interactions which, to date, remain largely undefined, and whose interspecific evolutionary conservation is unknown. This study applied Bayesian methods to illustrate the interrelationships between seminal profiles of interleukin (IL)-1alpha, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12 (p70), IL-13, IL-17, eotaxin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon (IFN)-gamma, keratinocyte-derived chemokine (KC), monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein (MIP-1) alpha, MIP-1beta, regulated on activation normal T cell expressed and secreted (RANTES), tumour necrosis factor (TNF)-alpha, leptin, inducible protein (IP)-10 and vascular endothelial growth factor (VEGF) in a rat model. IL-2, IL-9, IL-12 (p70), IL-13, IL-18, eotaxin, IFN-gamma, IP-10, KC, leptin, MCP-1, MIP-1alpha and TNF-alpha were significantly higher in serum, whilst IL-1beta, IL-5, IL-6, IL-10, IL-17, G-CSF and GM-CSF were significantly higher in seminal fluid. When compared to mouse profiles, only G-CSF was present at significantly higher levels in the seminal fluid in both species. Bayesian modelling highlighted key shared features across mouse and rat networks, namely TNF-alpha as the terminal node in both serum and seminal plasma, and MCP-1 as a central coordinator of seminal cytokine networks through the intermediary of KC and RANTES. These findings reveal a marked interspecific conservation of seminal cytokine networks

Current issues in medically assisted reproduction and genetics in Europe: research, clinical practice, ethics, legal issues and policy. European Society of Human Genetics and European Society of Human Reproduction and Embryology.

In March 2005, a group of experts from the European Society of Human Genetics and European Society of Human Reproduction and Embryology met to discuss the interface between genetics and assisted reproductive technology (ART), and published an extended background paper, recommendations and two Editorials. Seven years later, in March 2012, a follow-up interdisciplinary workshop was held, involving representatives of both professional societies, including experts from the European Union Eurogentest2 Coordination Action Project. The main goal of this meeting was to discuss developments at the interface between clinical genetics and ARTs. As more genetic causes of reproductive failure are now recognised and an increasing number of patients undergo testing of their genome before conception, either in regular health care or in the context of direct-to-consumer testing, the need for genetic counselling and preimplantation genetic diagnosis (PGD) may increase. Preimplantation genetic screening (PGS) thus far does not have evidence from randomised clinical trials to substantiate that the technique is both effective and efficient. Whole-genome sequencing may create greater challenges both in the technological and interpretational domains, and requires further reflection about the ethics of genetic testing in ART and PGD/PGS. Diagnostic laboratories should be reporting their results according to internationally accepted accreditation standards (International Standards Organisation - ISO 15189). Further studies are needed in order to address issues related to the impact of ART on epigenetic reprogramming of the early embryo. The legal landscape regarding assisted reproduction is evolving but still remains very heterogeneous and often contradictory. The lack of legal harmonisation and uneven access to infertility treatment and PGD/PGS fosters considerable cross-border reproductive care in Europe and beyond. The aim of this paper is to complement previous publications and provide an update of selected topics that have evolved since 2005

Alteration of gene expression in human cumulus cells as a potential indicator of oocyte aneuploidy.

BACKGROUND: Human female meiosis is particularly error prone, leading to the generation of aneuploidy, a problem which increases dramatically with advancing age. Despite being of great clinical importance, the genesis of oocyte aneuploidy remains poorly understood. Cumulus cells (CCs) surround oocytes in antral follicles and play a crucial role in regulating their maturation. During this investigation, we aimed to obtain an insight into the follicular environment of oocytes that become aneuploid and identify non-invasive markers of oocyte chromosome status and competence. METHODS: Microarray comparative genomic hybridization was used to assess oocyte ploidy. Expression of 96 genes was examined via a large real-time PCR experiment in 51 CC samples, whereas an additional 26 CC clumps were used for a more focused real-time PCR experiment assessing just three genes. Gene selection was based on the results of a previous microarray analysis comparing the transcriptome of CCs from normal and aneuploid oocytes. RESULTS: Fifty eight of the investigated genes were confirmed to be expressed in CCs. Patterns of expression were generally similar among all CC samples, regardless of the chromosomal status of the corresponding oocyte. However, two genes, SPSB2 and TP53I3, were both significantly down-regulated in CCs from chromosomally abnormal oocytes (P<0.05). The expression of SPSB2 was also found to display a strong trend towards up-regulation in the CCs of oocytes that produced a healthy live birth (P=0.054). CONCLUSIONS: In the current study, SPSB2 and TP53I3 exhibited highly significant differences in their expression between CCs of normal and chromosomally abnormal oocytes. SPSB2 is involved in intracellular signalling and homeostasis, whereas TP53I3 regulates carbohydrate metabolism and apoptosis. We speculate that both these genes might have the potential to serve as non-invasive markers of oocyte aneuploidy

Aproximación al manejo y composición de los residuos de construcción y demolición en Lima Metropolitana

Dentro de la amplia gama de desechos que produce la ciudad, la generación de residuos de construcción y de demolición, y su adecuada disposición, es uno de los menos atendidos. Esta investigación se plantea estudiar el estado de composición y manejo de los residuos de construcción y demolición en Lima Metropolitana, con el propósito de obtener información que sirva para tomar decisiones de política y establecer normas en los sectores público y privado. El fin es mejorar la gestión de dichos residuos, aminorar los impactos medioambientales y lograr beneficios económicos

Regulation of interleukin-8 expression in human endometrial endothelial cells: a potential mechanism for the pathogenesis of endometriosis.

The elevation of the proinflammatory chemoattractant cytokine levels in ectopic and eutopic endometrium of endometriosis implies an inflammatory basis for this disease. The relationship between endothelial cells and leukocytes is likely to be important in the regulation of inflammatory mediators of endometriosis. The aim of this study was to describe the temporal and spatial expression of IL-8 in human endometrial endothelial cells (HEEC) in vivo and to compare the in vitro regulation of IL-8 expression by sex steroids in HEEC from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to menstrual cycle phase and examined by immunohistochemistry for IL-8 expression. Endothelial cells of endometriotic implants expressed higher IL-8 immunoreactivity compared with endothelial cells of eutopic endometrium from women with or without endometriosis ( P < 0.02). For in vitro studies, HEEC were isolated from women with or without endometriosis and grown to preconfluence. The purity of cultured HEEC ( 90 - 95%) was confirmed by immunocytochemistry using endothelium-specific markers, CD31 and CD146. The effects of estradiol ( 5 x 10(-8) M), progesterone (10 (-7) M), or both on IL-8 mRNA and protein levels were analyzed by RT-PCR and ELISA, respectively. Sex steroids reduced the expression of IL-8 mRNA and protein in HEEC from women without endometriosis. In contrast, both estradiol and progesterone stimulated IL-8 mRNA and protein expression in HEEC from women with endometriosis. We postulate that the stimulation of chemokine expression by sex steroids in HEEC of women with endometriosis may play a role in the inflammatory aspect of this disease

Cadmium-induced changes in epithelial cells of the rat stomach

WOS: 000165101700007PubMed ID: 11097472The aim of this study was to determine the changes in the function and fine structure of the gastric mucosa following exposure to high cadmium (Cd) for 30 d in rats. in the present study, control animals were fed with normal food and tap water and the remaining animals received Cd (15 ppm CdCl2) in drinking water for the same period. Receiving Cd for 30 d increased the mean blood (p < 0.01) and mucosa (p < 0.001) Cd levels, while decreased mucus thickness, mucin content (p < 0.01) significantly. Basal acid output fell significantly (p < 0.01). Light and electron microscopic examination revealed the following: (1) Cd decreases the mean number of surface mucous, isthmic-neck, parietal cells (p < 0.05) and chief cells (p < 0.001) per unit from the control value and (2) in some cells of zymogenic unit, the Cd-induced alterations were characterized with dilated Golgi cisternae, focal enlarged endoplsmic reticulum, broken tubulovesicles, degenerated mitochondria, dense nuclei, as well as lysosomal structures. We concluded that Cd augments the elimination rate of zymogenic unit's cells by increasing the alteration rate, and the reduced basal acid output, mucin content, and mucus thickness can be explained easily with the loss of zymogenic unit's cell population