Biomedical subjects

Franco Mangia

Publications and source records attributed to Franco Mangia.

7 recordsLinked to original sources

PubMed2005

Enhancement of mouse sperm motility by the PI3-kinase inhibitor LY294002 does not result in toxic effects on preimplantation embryo development.

BACKGROUND: A reduced number of progressively motile sperm (as may occur in cases of asthenozoospermia or when cryopreserved spermatozoa are used for fertilization) limits the possibility of applying various assisted reproductive techniques (ARTs). We previously showed that incubation of sperm with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 increases sperm progressive motility and enhances the number of sperm recovered by capacitation protocols used in ART. METHODS AND RESULTS: In the present study, we investigate the motility-enhancing effects of this compound in epididymal mouse sperm, and examine the use of the mouse system to investigate the effect of LY294002 on oocyte fertilization and preimplantation embryo development. Our results show that neither pre-incubation of mouse spermatozoa with the inhibitor during in vitro capacitation nor the direct addition of LY294002 to the sperm-oocyte mixture significantly affects the process of fertilization and preimplantation development of embryos produced even when they developed in the presence of LY294002. CONCLUSIONS: The present data encourage the design of new drugs based on the molecular structure of LY294002, which may open up new options for the in vitro treatment of human/animal asthenozoospermia.

Animals↗

PubMed2005

Thg-1 pit gene expression in granule cells of the developing mouse brain and in their synaptic targets, mature Purkinje, and mitral cells.

We have studied the expression of Thg-1 pit in developing and adult mouse brain by in situ hybridization analysis. We show that, at day 12.5 of embryo development, Thg-1 pit expression is restricted to the rhombic lip, subventricular neuroepithelium/mantle zone, and lateral ganglionic eminence, namely the embryonic brain areas where granule cell precursors originate. Thereafter, Thg-1 pit expression landmarks both differentiative steps and the mature function of granule/interneuron cells in several brain districts, including cerebellum, basal forebrain, olfactory bulb, and hippocampus. In the adult, Thg-1 pit becomes also activated in mitral cells of olfactory bulb and in Purkinje cells of cerebellum, in concomitance with full development of the synaptic contacts that Purkinje and mitral cells establish with granule cells. We conclude that Thg-1 pit is relevant to specification, proliferation/migration, differentiation, and mature function of granule/interneuron cells in different brain districts, as well as to the function of mature, but not immature, Purkinje cells and mitral cells.

Aging↗

PubMed2005

PHGPx in spermatogenesis: how many functions?

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique intracellular enzyme that directly reduces lipid hydroperoxides in membranes and has the ability to use protein thiol groups as donor substrates. Three isoforms of PHGPx have so far been identified, namely, a mitochondrial, a cytosolic and a nuclear variant. This article is focused on recent evidence demonstrating that (1) mitochondrial and nuclear PHGPx isoforms display a different pattern of expression during male germ cell differentiation; (2) different PHGPx isoforms play specific and independent functions during sperm maturation. The data are discussed in light of the idea that PHGPx is a moonlighting protein, changing roles depending on the intracellular localization, expression in a specific cell type and different partners which it interacts with.

Animals↗

PubMed2004

Anxiety-related behaviour in C57BL/6 <--> BALB/c chimeric mice.

In a previous study on anxiety-related behaviours of the genetically and behaviourally distant inbred mouse strains C57BL/6 and BALB/c using the Elevated plus-maze (EPM) and Open-field (OF) apparatuses, we identified a number of variables, the factorial scores of which were grouped by principal component analysis (PCA) into factors specifically describing each inbred strain. We have now studied the effect of C57BL/6 and BALB/c haploid sets of genes on this behaviour by comparing EPM and OF variables of C57BL/6 and BALB/c versus C57BL/6 x BALB/c F1 hybrids (B6CBF1) and chimeric C57BL/6 x BALB/c (CHIM) mice. CHIM mice were made by embryo aggregation and the chimerism degree of their brain was inferred from coat black/white distribution. Discriminant analysis of EPM and OF factorial scores of C57BL/6, BALB/c and CHIM mice showed that CHIM mice with an exceeding (> or =80%) C57BL/6 or BALB/c coat component had behaviours similar to those of the predominant strain, whereas CHIM mice with intermediate chimerism differed from both inbred strains. Additional MANOVA analysis showed that the anxiety behaviour of CHIM mice with intermediate chimerism was similar to that of B6CBF1 mice as for factors not describing the inbred strains, including a motor activity mostly limited to protected areas, with attempts to approach the anxiogenic areas while processing/storing the external information. We conclude that the balanced presence of both C57BL/6 and BALB/c genetic backgrounds, either when carried by the same cell or by different cells, gives rise to a novel stress coping strategy described by factors different from those of the inbred strains.

Animals↗

PubMed2004

Early transcriptional activation of the hsp70.1 gene by osmotic stress in one-cell embryos of the mouse.

In fertilized mouse eggs, de novo transcription of embryonic genes is first observed during the S phase of the one-cell stage. This transcription, however, is mostly limited to the male pronucleus and possibly uncoupled from translation, making the functional meaning obscure. We found that one-cell mouse embryos respond to the osmotic shock of in vitro isolation with migration of HSF1, the canonical stress activator of mammalian heat shock genes, to pronuclei and by transient transcription of the hsp70.1, but not hsp70.3 and hsp90, heat shock genes. Isolated growing dictyate oocytes also display a nuclear HSF1 localization, but, in contrast with embryos, they transcribe both hsp70.1 and hsp70.3 genes only after heat shock. Intranuclear injection of double-stranded oligodeoxyribonucleotides containing HSE, GAGA box or GC box consensus sequences, and antibodies raised to transcription factors HSF1, HSF2, Drosophila melanogaster GAGA factor, or Sp1 demonstrated that hsp70.1 transcription depends on HSF1 in both oocytes and embryos and that Sp1 is dispensable in oocytes and inhibitory in the embryos. Hsp70.1 thus represents the first endogenous gene so far identified to be physiologically activated and tightly regulated after fertilization in mammals.

Animals↗

PubMed2002

Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice.

The elevated plus-maze test (PM) and open-field test (OF) are routinely used to study anxiety-related behaviour in mouse. However, the data obtained with these tests have often been contradictory, probably because of differences between laboratories in the selection and analysis of behavioural parameters. We have characterised the pattern of mouse anxiety by analysing a number of behavioural parameters with both PM and OF in BALB/c and C57BL/6 mice, two behaviourally distant mouse strains. Twenty-eight variables (15 analysed with PM and 13 with OF) were selected by correlation analysis from those initially recorded with both tests. The scores of the selected variables were first analysed by MANOVAs, and then by principal component analysis (PCA). PCA extracted five factors for PM and four factors for OF. These factors were subjected to a correlation analysis, which showed significant correlation between four of them. The factorial scores of BALB/c and C57BL/6 mice were analysed by MANOVAs, which showed significant effects of both the strain and test used. Our results confirm the multidimensional structure of mouse anxiety-related behaviour as regards both simple components and functional interactions, and comprehensively represent strain- and test-specific features of mouse anxiety-related behaviour.

Animals↗

PubMed2002

TCL1 participates in early embryonic development and is overexpressed in human seminomas.

Overexpression of the TCL1 oncogene has been shown to play a causative role in T cell leukemias of humans and mice. The characterization of Tcl1-deficient mice in these studies indicates an important developmental role for Tcl1 in early embryogenesis. In wild-type embryos, Tcl1 is abundant in the first three mitotic cycles, during which it shuttles between nuclei and the embryo cortical regions in a cell-cycle-dependent fashion. The absence of this protein in early embryogenesis results in reduced fertility of female mice. The present studies elucidate the mechanism responsible for the reduced female fertility through analysis of the oogenesis stages and early embryo development in Tcl1-deficient mice. Even though Tcl1(-/-) females display normal oogenesis and rates of oocyte maturation/ovulation and fertilization, the lack of maternally derived Tcl1 impairs the embryo's ability to undergo normal cleavage and develop to the morula stage, especially under in vitro culture conditions. Beyond this crisis point, differentiative traits of zygotic genome activation and embryo compaction can take place normally. In contrast with this unanticipated role in early embryogenesis, we observed an overexpression of TCL1 in human seminomas. This finding suggests that TCL1 dysregulation could contribute to the development of this germinal cell cancer as well as lymphoid malignancies.

Animals↗