190 research outputs found

    Long-term, low-dose lead exposure alters the gonadotropin-releasing hormone system in the male rat.

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    Lead is a male reproductive toxicant. Data suggest that rats dosed with relatively high levels of lead acetate for short periods of time induced changes in the hypothalamic gonadotropin-releasing hormone (GnRH) at the molecular level, but these changes were attenuated with increased concentration of exposure. The current study evaluated whether exposure to low levels of lead acetate over longer periods of time would produce a similar pattern of adaptation to toxicity at the molecular and biologic levels. Adult 100-day-old Sprague-Dawley male rats were dosed with 0, 0.025, 0.05, 0.1, and 0.3% lead acetate in water. Animals were killed after 1, 4, 8, and 16 weeks of treatment. Luteinzing hormone (LH) and GnRH levels were measured in serum, and lead levels were quantified in whole blood. Hypothalamic GnRH mRNA levels were also quantified. We found no significant differences in serum LH and GnRH among the groups of animals treated within each time period. A significant dose-related increase of GnRH mRNA concentrations with lead dosing occurred in animals treated for 1 week. Animals treated for more than 1 week also exhibited a significant increase in GnRH mRNA, but with an attenuation of the increase at the higher concentrations of lead with increased duration of exposure. We conclude that the signals within and between the hypothalamus and pituitary gland appear to be disrupted by long-term, low-dose lead exposure

    More than just hormones: H295R cells as predictors of reproductive toxicity

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    AbstractMany of the commonly observed reproductive toxicities associated with therapeutic compounds can be traced to a disruption of the steroidogenic pathway. We sought to develop an in vitro assay that would predict reproductive toxicity and be high throughput in nature. H295R cells, previously validated as having an intact and functional steroidogenic pathway, were treated with 83 known-positive and 79 known-negative proprietary and public-domain compounds. The assay measured the expression of the key enzymes STAR, 3ÎČHSD2, CYP17A1, CYP11B2, CYP19A1, CYP21A2, and CYP11A1 and the hormones DHEA, progesterone, testosterone, and cortisol. We found that a Random Forest model yielded a receiver operating characteristic area under the curve (ROC AUC) of 0.845, with sensitivity of 0.724 and specificity of 0.758 for predicting in vivo reproductive toxicity with this in vitro assay system

    PETAAL Protection of border tree environment and technology

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    The sycamore lace bug has been identified as one of the main phytosanitary problems for managers of tree-planted heritage sites within green areas in 36,000 French regional authorities. The spread of this pest nationally and the predominance of sycamores in towns makes the bug one of the first pests to receive phytosanitary intervention in our green spaces. The move from chemical control, which is currently used, to biological control is governed by environmental and societal issues and embodies ongoing major technical innovation within green areas

    The pesticide methoxychlor given orally during the perinatal/juvenile period, reduced the spermatogenic potential of males as adults by reducing their Sertoli cell number

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    Perinatal and juvenile oral treatment of rats with the insecticide, methoxychlor (MXC), reduced testicular size and other reproductive indices including the number of epididymal spermatozoa in those animals as adults [6]. The objective was to determine if these males exposed during development had fewer Sertoli cells which might explain these testicular effects. Rat dams were gavaged with MXC at 0, 5, 50, or 150 mg.kg(-1).day(-1) for the week before and after they gave birth. Resulting male pups (15/group) then were dosed directly from postnatal day 7 to 42. Testes were fixed in Bouin's and in OsO4, embedded in Epon and sectioned at 0.5 mum, stained with toluidine blue, and evaluated stereologically or cut at 20 mm to measure Sertoli cell nuclei with Nomarski optics. Sertoli cell number was calculated as the volume density of the nucleus times the parenchymal weight (90% of testicular weight) divided by the volume of a single Sertoli cell nucleus. Across dose groups, there were no changes in the nuclear volume density, the volume of a single nucleus, or the number of Sertoli cells per g parenchyma. There were highly significant dose-related changes in the volume of Sertoli cell nuclei per testis and the number of Sertoli cells per testis. Reduced testicular weight (r = 0.94) and reduced numbers of epididymal spermatozoa (r = 0.43) were significantly (p < 0.01) correlated to reduced number of Sertoli cells per testis. Hence, perinatal and juvenile oral exposure to MXC can reduce spermatogenic potential of males as adults by reducing their number of Sertoli cells

    Programme PETAAL : Une stratégie combinée de protection biologique contre le tigre du platane en espaces verts

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    "Le végétal fait campagne" ou comment faire face à un monde de plus en plus urbanisé

    Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

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    The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches

    Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

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    The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches
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