In vivo effects of chronic contamination with 137 cesium on testicular and adrenal steroidogenesis

More than 20 years after Chernobyl nuclear power plant explosion, radionuclids are still mainly bound to the organic soil layers. The radiation exposure is dominated by the external exposure to gamma-radiation following the decay of 137Cs and by soil-to-plant-to-human transfer of 137Cs into the food chain. Because of this persistence of contamination with 137Cs, questions regarding public health for people living in contaminated areas were raised. We investigated the biological effects of chronic exposure to 137Cs on testicular and adrenal steroidogenesis metabolisms in rat. Animals were exposed to radionuclide in their drinking water for 9 months at a dose of 6,500 Bq/l (610 Bq/kg/day). Cesium contamination decreases the level of circulating 17β-estradiol, and increases corticosterone level. In testis, several nuclear receptors messenger expression is disrupted; levels of mRNA encoding Liver X receptor α (LXRα) and LXRβ are increased, whereas farnesoid X receptor mRNA presents a lower level. Adrenal metabolism presents a paradoxical decrease in cyp11a1 gene expression. In conclusion, our results show for the first time molecular and hormonal modifications in testicular and adrenal steroidogenic metabolism, induced by chronic contamination with low doses of 137Cs. © 2007 Springer-Verlag

Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism in rat

Uranium is a naturally occurring heavy metal found in the Earth's crust. It is an alpha-emitter radioactive element from the actinide group that presents both radiotoxicant and chemotoxicant properties. Some studies revealed that uranium could affect the reproductive system. To distinguish chemical versus radiological effects of uranium on the metabolism of the steroids in the testis, rats were contaminated via their drinking water with depleted or enriched uranium. Animals were exposed to radionuclides for 9 months at a dose of 40 mg/L (560 Bq/L for depleted uranium, 1680 Bq/L for enriched uranium). Whereas depleted uranium did not seem to significantly affect the production of testicular steroid hormones in rats, enriched uranium significantly increased the level of circulating testosterone by 2.5-fold. Enriched uranium contamination led to significant increases in the mRNA levels of StAR (Steroidogenic Acute Regulatory protein; 3-fold, p =.001), cyp11a1 (cytochrome P45011a1; 2.2-fold, p <.001), cyp17a1 (cytochrome P45017a1; 2.5-fold, p =.014), cyp19a1 (cytochrome P45019a1; 2.3-fold, p =.021), and 5α -R1 (5α reductase type 1; 2.0-fold, p =.02), whereas depleted uranium contamination induces no changes in the expression of these genes. Moreover, expression levels of the nuclear receptors LXR (Liver X Receptor) and SF-1 (Steroidogenic Factor 1), as well as the transcription factor GATA-4, were modified following enriched uranium contamination. Altogether, these results show for the first time a differential effect among depleted or enriched uranium contamination on testicular steroidogenesis. It appears that the deleterious effects of uranium are mainly due to the radiological activity of the compound. Copyright © American College of Toxicology

Les oxystérols: Métabolisme, rôles biologiques et pathologies associées

Les oxystérols ou hydroxycholestérols sont des molécules d’origine biologique ou chimique produites par oxydation ou hydroxylation du cholestérol. Ce sont des composés ayant un rôle important en physiologie et en physiopathologie chez les mammifères [1]. Certains oxystérols sont considérés comme des molécules de signalisation pouvant avoir une action régulatrice dans plusieurs métabolismes comme la biosynthèse du cholestérol, des hormones stéroïdiennes et des acides biliaires. D’autres oxystérols, par contre, sont considérés comme des composés toxiques pouvant induire des perturbations structurales et métaboliques au sein des cellules avec comme conséquence, le renforcement de pathologies comme la lithiase biliaire cholestérolique et l’athérosclérose. Enfin, plusieurs oxystérolssemblent également capables de perturber des mécanismes biologiques comme le processus inflammatoire [2]. Dans cette revue seront mises en avant les dernières connaissances concernant les propriétés et effets biologiques des oxystérols avec le souci de distinguer dans leurs effets, et par analogie avec le cholestérol, les « bons » et les « mauvais » oxystérols. La dernière partie de cette présentation décrira leur lien avec plusieurs pathologies

Low dose of uranium induces multigenerational epigenetic effects in rat kidney

International audiencePurpose A protocol of chronic exposure to low dose of uranium was established in order to distinguish the sexual differences and the developmental process that are critical windows for epigenetic effects over generations. Methods Both male and female rats were contaminated through their drinking water with a non-toxic solution of uranyl nitrate for 9 months. The exposed generation (F0) and the following two generations (F1 and F2) were examined. Clinical monitoring, global DNA methylation profile and DNA methyltransferases (DNMTs) gene expression were analyzed in kidneys. Results While the body weight of F1 males increased, a small decrease in kidney and body weight was observed in F2 males. In addition, global DNA hypermethylation profile in kidney cells was observed in F1 and F2 males. qPCR results reveal a significant increase of methyltransferase genes expression (DNMT1 and DNMT3a) for F2 females. Conclusions In the field of public health policy and to raise attention to generational effects for the risk assessment of the environmental exposures, low doses of uranium do not imply clinical effects on adult exposed rats. However, our results confirm the importance of the developmental windows’ sensitivity in addition to the sexual dimorphisms of the offspring. © 2018, Copyright © 2018 Taylor and Francis Group LLC