Organ transformation by environmental disruption of protein integrity and epigenetic memory in Drosophila.

Despite significant progress in understanding epigenetic reprogramming of cells, the mechanistic basis of "organ reprogramming" by (epi-)gene-environment interactions remained largely obscure. Here, we use the ether-induced haltere-to-wing transformations in Drosophila as a model for epigenetic "reprogramming" at the whole organism level. Our findings support a mechanistic chain of events explaining why and how brief embryonic exposure to ether leads to haltere-to-wing transformations manifested at the larval stage and on.

Protocol for studying microbiome impact on host energy and reproduction in .

gut microbiome in flies has been shown to have a systemic influence on energy production by the host and the energetic investment in growth and reproduction. Here we describe a protocol for studying the mechanisms responsible for this remote regulation by gut bacteria. This protocol enables whole-body and ovary-specific quantification of energy-storing molecules as well as identification of host metabolites and pathways that are regulated by gut microbiome-derived factors.

Systemic Regulation of Host Energy and Oogenesis by Microbiome-Derived Mitochondrial Coenzymes.

Gut microbiota have been shown to promote oogenesis and fecundity, but the mechanistic basis of remote influence on oogenesis remained unknown. Here, we report a systemic mechanism of influence mediated by bacterial-derived supply of mitochondrial coenzymes. Removal of microbiota decreased mitochondrial activity and ATP levels in the whole-body and ovary, resulting in repressed oogenesis.

Impact of gut microbiota on the fly's germ line.

Unlike vertically transmitted endosymbionts, which have broad effects on their host's germ line, the extracellular gut microbiota is transmitted horizontally and is not known to influence the germ line. Here we provide evidence supporting the influence of these gut bacteria on the germ line of Drosophila melanogaster. Removal of the gut bacteria represses oogenesis, expedites maternal-to-zygotic-transition in the offspring and unmasks hidden phenotypic variation in mutants.

Implantation: mutual activity of sex steroid hormones and the immune system guarantee the maternal-embryo interaction.

Implantation is strictly dependent on the mutual interaction between a receptive endometrium and the blastocyst. Hence, synchronization between blastocyst development and the acquisition of endometrial receptivity is a prerequisite for the success of this process. This review depicts the cellular and molecular events that coordinate these complex activities.

The role of inflammation for a successful implantation.

Approximately half of all human embryo implantations result in failed pregnancy. Multiple factors may contribute to this failure, including genetic or metabolic abnormalities of the embryo. However, many of these spontaneous early abortion cases are attributed to poor uterine receptivity.

An in vitro model for the study of human implantation.

Problem: Implantation remains the rate-limiting step for the success of in vitro fertilization. Appropriate models to study the molecular aspects of human implantation are necessary in order to improve fertility.

Methods: First trimester trophoblast cells are differentiated into blastocyst-like spheroids (BLS) by culturing them in low attachment plates.

Local injury of the endometrium induces an inflammatory response that promotes successful implantation.

Objective: To study whether an injury-induced inflammation might be the mechanism underlying the favorable effect of endometrial biopsy on the implantation rate in in vitro fertilization (IVF) patients.

Design: Controlled clinical study.

Setting: A medical center IVF unit and a research institute.

Inflammation and implantation.

Approximately half of all human embryo implantations result in failed pregnancy. Multiple factors may contribute to this failure, including genetic or metabolic abnormalities of the embryo. However, many of these spontaneous early abortion cases are attributed to poor uterine receptivity.

Endometrial biopsy-induced gene modulation: first evidence for the expression of bladder-transmembranal uroplakin Ib in human endometrium.

Objective: To explore the possibility that endometrial injury modulates the expression of specific genes that may increase uterine receptivity.

Design: Controlled clinical study.

Setting: Clinical IVF unit and academic research center.

Involvement of the tyrosine phosphatase early gene of liver regeneration (PRL-1) in cell cycle and in liver regeneration and fibrosis effect of halofuginone.

Tyrosine phosphatase PRL-1 is one of the immediate-early genes up-regulated during liver regeneration and is apparently involved in cell proliferation. Previously, we have demonstrated that halofuginone, an inhibitor of collagen type I synthesis, prevents liver fibrosis and improves cirrhotic liver regeneration. In this study, we evaluated the effect of halofuginone on PRL-1 expression, its cellular localization in vitro and during liver regeneration, and fibrosis progression in vivo.

Halofuginone, an inhibitor of collagen synthesis by rat stellate cells, stimulates insulin-like growth factor binding protein-1 synthesis by hepatocytes.

Background/aims: Halofuginone, an inhibitor of collagen synthesis, prevented and caused resolution of established hepatic fibrosis. A genomic approach in vivo was used to search for additional genes responsible for halofuginone mode of action.

Methods: Fibrosis was induced in rats by thioacetamide (TAA) and evaluated by collagen type I gene expression and the levels of collagen, tissue inhibitors of metalloproteinases-2 and smooth-muscle actin.