Pioglitazone in adult rats reverses immediate postnatal overfeeding-induced metabolic, hormonal, and inflammatory alterations

International audienceImmediate postnatal overfeeding in rats, obtained by reducing the litter size, results in early-onset obesity. Such experimental paradigm programs overweight, insulin resistance, dyslipidemia, increased adipose glucocorticoid metabolism [up-regulation of glucocorticoid receptor (GR) and 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1)], and overexpression of proinflammatory cytokines in mesenteric adipose tissue (MAT) in adulthood. We studied the effects of pioglitazone, a PPAR gamma agonist, treatment on the above-mentioned overfeeding-induced alterations. Nine-month-old rats normofed or overfed during the immediate postnatal period were given pioglitazone (3 mg/kg/day) for 6 weeks. Pioglitazone stimulated weight gain and induced a redistribution of adipose tissue toward epididymal location with enhanced plasma adiponectin. Treatment normalized postnatal overfeeding-induced metabolic alterations (increased fasting insulinemia and free fatty acids) and mesenteric overexpression of GR, 11 beta-HSD11, CD 68, and proinflammatory cytokines mRNAs, including plasminogen-activator inhibitor type 1. MesentericGRmRNAlevels correlated positively with mesenteric proinflammatory cytokinesmRNAconcentrations. In vitro incubation of MAT obtained from overfed rats demonstrated that pioglitazone induced a down-regulation of GR gene expression and normalized glucocorticoid-induced stimulation of 11 beta-HSD1 and plasminogen-activator inhibitor type 1 mRNAs. Our data show for the first time that the metabolic, endocrine, and inflammatory alterations induced by early-onset postnatal obesity can be reversed by pioglitazone at the adulthood. They demonstrate that pioglitazone, in addition to its well-established effect on adipose tissue redistribution and adiponectin secretion, reverses programing-induced adipose GR, 11 beta-HSD1, and proinflammatory cytokines overexpression, possibly through a GR-dependent mechanism

A new approach for the oocyte genotoxicity assay: adaptation of comet assay on mouse cumulus-oocyte complexes

International audienceConventional genotoxicity tests are technically difficult to apply to oocytes, and results obtained on somatic cells cannot be extrapolated to gametes. We have previously described a comet assay (original-CA) on denuded mouse oocytes, but, invivo, oocytes are not isolated from their surrounding follicular cells. Our objective was to develop a comet assay on cumulus-oocyte complexes (COC-CA) for a more physiological approach to study the genotoxicity of environmental factors on oocytes. For COC-CA, whole COC were exposed directly to exogenous agents after ovulation and removal from oviducts. Three conditions were studied: a negative control group, and two positive control groups, one of which was exposed to hydrogen peroxide (H2O2) and the other group was incubated with cerium dioxide nanoparticles (CeO2 NPs). With both tests, DNA damage was significant in the presence of both H2O2 and CeO2 NPs compared with the negative control. COC-CA offers an interesting tool for assaying the genotoxicity of environmental agents towards germinal cells. Furthermore, COC-CA is less time-consuming and simplifies the protocol of the original-CA, because COC-CA is easier to perform without the washing-out procedure

Very low concentration of cerium dioxide nanoparticles induce DNA damage, but no loss of vitality, in human spermatozoa

International audienceCerium dioxide nanoparticles (CeO 2 NP) are widely used for industrial purposes, as in diesel, paint, wood stain and as potential therapeutic applications. The Organization for Economic Cooperation and Development included CeO 2 NP in the priority list of nanomaterials requiring urgent evaluation. As metal nanoparticles can cross the blood-testis barrier, CeO 2 NP could interact with spermatozoa. The genotoxicity of CeO 2 NP was demonstrated in vitro on human cell lines and mouse gametes. However, the effects of CeO 2 NP on human spermatozoa DNA remain unknown. We showed significant DNA damage induced in vitro by CeO 2 NP on human spermatozoa using Comet assay. The genotoxicity was inversely proportional to the concentration (0.01 to 10 mg·L −1). TEM showed no internalization of CeO 2 NP into the spermatozoa. This study shows for the first time that in vitro exposure to very low concentrations of cerium dioxide nanoparticles can induce significant DNA damage in human spermatozoa. These results add new and important insights regarding the reproductive toxicity of priority nanomaterials, which require urgent evaluation

In vivo exposure to benzo(a)pyrene induces significant DNA damage in mouse oocytes and cumulus cells

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Fine atmospheric particles emitted by industrial, traffic and urban sources in France : characterization and genotoxicity.

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Focus sur le système endocannabinoïde et la reprotoxicité du cannabis chez la femme à l’heure du débat sur sa dépénalisation en France

International audienceAmong recreative compounds, marijuana is the most used worldwide. Delta9THC binding on brain endocannabinoid receptors drives its psychotropic effects. The endocannabinoid system (ECS) is an endogenous neurohormonal system essential for homeostasis composed of ligands, metabolic enzymes and at least 2 receptors discovered to date. In female reproduction, the ECS regulates the hypothalamic-pituitary axis and many steps of the reproduction process, such as ovulation, tubal transportation and trophoblast implantation. Delta9THC can cross the placental barrier and bind to the fetal endocannabinoid system. In humans, fetal and obstetrical consequences of marijuana use during pregnancy are intrauterine growth restriction and preterm delivery. In the light of legalization projects currently reviewed in several western countries, further research should be conducted to improve knowledge on maternal, fetal and reprotoxic consequences of marijuana use during reproductive age and pregnancy.Le cannabis est le psychotrope récréatif le plus utilisé dans le monde. Les effets recherchés sont obtenus par l’action du delta9THC sur les récepteurs cérébraux du système endocannabinoïde. Le système endocannabinoïde est indispensable à l’homéostasie de l’organisme. Il est composé d’un ensemble de récepteurs, ligands endogènes et d’enzymes de son métabolisme distribués de manière ubiquitaire dans l’organisme. Chez la femme, il participe à la régulation de nombreuses étapes du processus de reproduction : régulation de l’axe hypothalamohypophysaire, ovulation, transport tubaire, implantation trophoblastique. Le delta9THC, lipophile, traverse la barrière placentaire et peut se fixer sur le système endocannabinoïde fœtal qui apparaît précocement au cours du développement. Chez l’humain, les conséquences fœtales et obstétricales connues de la consommation de cannabis au cours de la grossesse sont principalement le retard de croissance et l’accouchement prématuré. Au vu des discussions actuellement menées dans plusieurs pays concernant la légalisation de la consommation de cannabis, de nouvelles recherches sont nécessaires pour en préciser les conséquences maternelles, fœtales et reprotoxiques

Comet assay on thawed embryos: An optimized technique to evaluate DNA damage in mouse embryos

International audienceOur objective was to optimize the CA technique on mammal embryos. Materials and methods: 1000 frozen 2-cell embryos from B6CBA mice were used. Based on a literature review, and after checking post-thaw embryo viability, the main outcome measures included: 1) comparison of the embryo recovery rate between 2 CA protocols (2 agarose layers and 3 agarose layers); 2) comparison of DNA damage by the CA on embryos with (ZP +) and without (ZP−) zona pellucida; and 3) comparison of DNA damage in embryos exposed to 2 genotoxic agents (H 2 O 2 and simulated sunlight irradiation (SSI)). DNA damage was quantified by the % tail DNA. Results: 1) The recovery rate was 3,3% (n = 5/150) with the 2 agarose layers protocol and 71,3% (n = 266/ 371) with the 3 agarose layers protocol. 2) DNA damage did not differ statistically significantly between ZP − and ZP+ embryos (12.60 ± 2.53% Tail DNA vs 11.04 ± 1.50 (p = 0.583) for the control group and 49.23 ± 4.16 vs 41.13 ± 4.31 (p = 0.182) for the H 2 O 2 group); 3) H 2 O 2 and SSI induced a statistically significant increase in DNA damage compared with the control group (41.13 ± 4.31% Tail DNA, 36.33 ± 3.02 and 11.04 ± 1.50 (p < 0.0001)). The CA on mammal embryos was optimized by using thawed embryos, by avoiding ZP removal and by the adjunction of a third agarose layer

Three-year National report from the Gruppo Italiano di Ortogeriatria (GIOG) in the management of hip-fractured patients

Background: Hip fractures (HF) are a major issue worldwide. We aimed at evaluating the practices in delivering care to patients with HF among several Italian Orthogeriatric centers. Methods: The study took place from February 2016 to July 2018. Seven performance indicators (pre-surgical cognitive assessment, surgery performed 64 48&nbsp;h from fracture, removal of urinary catheter/absence of delirium/start of physiotherapy on the first post-operative day, prescription of bone protection at discharge, and discharge toward rehabilitation) were collected. Results: The 14 participating hospitals totally recruited 3.017 patients. Patients were old (median age 86&nbsp;years; Inter Quartile Range [IQR] 80\u201390), mostly females (77%). Nearly 55% of them were already impaired in mobility and about 10% were nursing home residents. Median time-to-surgery was 41&nbsp;h (IQR 23\u201362). Models of care greatly varied among centers, only 49.3% of patients being co-managed by geriatricians and orthopedics. There was high variability across centers in four indicators (\u201cpre-surgical cognitive assessment\u201d, \u201cbone protection prescription\u201d, \u201cuse of urinary catheter\u201d and \u201cstart of physiotherapy\u201d), moderate in two indicators (\u201csurgery performed 64 48&nbsp;h from fracture\u201d and \u201cdischarge toward rehabilitation\u201d and low in one (\u201cabsence of delirium on day following surgery\u201d). Comparison with international studies suggests very different ways of providing care to HF Italian patients. Conclusions: The study results suggest high inter-center variability in the key-performance indicators, and different approaches in providing care to our HF patients in comparison to other countries. A National debate on the topic is required in Italy to harmonize practices of orthogeriatric care