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Meng Tang - One of the best experts on this subject based on the ideXlab platform.
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Reproductive Toxicity induced by nickel nanoparticles in Caenorhabditis elegans.
Environmental toxicology, 2016Co-Authors: Lu Kong, Xiaojie Gao, Jiaqian Zhu, Ting Zhang, Yuying Xue, Meng TangAbstract:To investigate the Reproductive Toxicity and underlying mechanism of nickel nanoparticles (Ni NPs), Caenorhabditis elegans (C. elegans) were treated with/without 1.0, 2.5, and 5.0 μg cm−2 of Ni NPs or nickel microparticles (Ni MPs). Generation time, fertilized egg numbers, spermatide activation and motility were detected. Results indicated, under the same treatment doses, that Ni NPs induced higher Reproductive Toxicity to C. elegans than Ni MPs. Reproductive toxicities observed in C. elegans included a decrease in brood size, fertilized egg and spermatide activation, but an increase in generation time and out-of-round spermatids. The Reproductive Toxicity of Ni NPs on C. elegans may be induced by oxidative stress. The Reproductive Toxicity in C. elegans induced by Ni NPs is consistent with our previous results in the rats. Therefore, C. elegans can be used as an alternative model to detect the early Reproductive Toxicity of Ni NPs exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
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Mechanisms involved in Reproductive Toxicity caused by nickel nanoparticle in female rats.
Environmental toxicology, 2016Co-Authors: Lu Kong, Xiaojie Gao, Jiaqian Zhu, Keping Cheng, Meng TangAbstract:Nickel nanoparticles (Ni NPs) are associated with Reproductive Toxicity. However, the mechanisms of Reproductive Toxicity are unclear. Our goal was to explore further Reproductive Toxicity induced by nickel nanoparticle and mechanisms involved in this process, including the role of oxidative stress and apoptosis. According to the one-generation Reproductive Toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including ultrastructural, reactive oxygen species (ROS), oxidant and antioxidant enzymes, and cell apoptosis-related factors. Ultrastructural results of ovaries showed mitochondrion swelling, disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum in the exposure groups. NiNPs had significantly decreased the activity of SOD and CAT, and had increased the levels of ROS, MDA, and NO in comparison with the control groups. The mRNA expressions of caspase-3, caspase-8, and caspase-9 and the expressions of Fas, Cyt c, Bax, and Bid protein on the ovaries significantly increased. At the same time, the expressions of Bcl-2 protein were significantly decreased. Based on these results, oxidative stress and cell apoptosis may play the important roles in inducing Reproductive Toxicity after NiNPs treatment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1674-1683, 2016.
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Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats
International journal of molecular sciences, 2014Co-Authors: Lu Kong, Ting Zhang, Meng Tang, Dayong Wang, Chao Wei, Geyu LiangAbstract:Nickel is associated with Reproductive Toxicity. However, the Reproductive Toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and Reproductive Toxicity. According to the one-generation Reproductive Toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and Reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the Reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.
Lu Kong - One of the best experts on this subject based on the ideXlab platform.
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Reproductive Toxicity induced by nickel nanoparticles in Caenorhabditis elegans.
Environmental toxicology, 2016Co-Authors: Lu Kong, Xiaojie Gao, Jiaqian Zhu, Ting Zhang, Yuying Xue, Meng TangAbstract:To investigate the Reproductive Toxicity and underlying mechanism of nickel nanoparticles (Ni NPs), Caenorhabditis elegans (C. elegans) were treated with/without 1.0, 2.5, and 5.0 μg cm−2 of Ni NPs or nickel microparticles (Ni MPs). Generation time, fertilized egg numbers, spermatide activation and motility were detected. Results indicated, under the same treatment doses, that Ni NPs induced higher Reproductive Toxicity to C. elegans than Ni MPs. Reproductive toxicities observed in C. elegans included a decrease in brood size, fertilized egg and spermatide activation, but an increase in generation time and out-of-round spermatids. The Reproductive Toxicity of Ni NPs on C. elegans may be induced by oxidative stress. The Reproductive Toxicity in C. elegans induced by Ni NPs is consistent with our previous results in the rats. Therefore, C. elegans can be used as an alternative model to detect the early Reproductive Toxicity of Ni NPs exposure. © 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
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Mechanisms involved in Reproductive Toxicity caused by nickel nanoparticle in female rats.
Environmental toxicology, 2016Co-Authors: Lu Kong, Xiaojie Gao, Jiaqian Zhu, Keping Cheng, Meng TangAbstract:Nickel nanoparticles (Ni NPs) are associated with Reproductive Toxicity. However, the mechanisms of Reproductive Toxicity are unclear. Our goal was to explore further Reproductive Toxicity induced by nickel nanoparticle and mechanisms involved in this process, including the role of oxidative stress and apoptosis. According to the one-generation Reproductive Toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including ultrastructural, reactive oxygen species (ROS), oxidant and antioxidant enzymes, and cell apoptosis-related factors. Ultrastructural results of ovaries showed mitochondrion swelling, disappearance of mitochondrial cristae, and enlargement of the endoplasmic reticulum in the exposure groups. NiNPs had significantly decreased the activity of SOD and CAT, and had increased the levels of ROS, MDA, and NO in comparison with the control groups. The mRNA expressions of caspase-3, caspase-8, and caspase-9 and the expressions of Fas, Cyt c, Bax, and Bid protein on the ovaries significantly increased. At the same time, the expressions of Bcl-2 protein were significantly decreased. Based on these results, oxidative stress and cell apoptosis may play the important roles in inducing Reproductive Toxicity after NiNPs treatment. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1674-1683, 2016.
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Nickel Nanoparticles Exposure and Reproductive Toxicity in Healthy Adult Rats
International journal of molecular sciences, 2014Co-Authors: Lu Kong, Ting Zhang, Meng Tang, Dayong Wang, Chao Wei, Geyu LiangAbstract:Nickel is associated with Reproductive Toxicity. However, the Reproductive Toxicity of nickel nanoparticles (Ni NPs) is unclear. Our goal was to determine the association between nickel nanoparticle exposure and Reproductive Toxicity. According to the one-generation Reproductive Toxicity standard, rats were exposed to nickel nanoparticles by gavage and we selected indicators including sex hormone levels, sperm motility, histopathology, and Reproductive outcome etc. Experimental results showed nickel nanoparticles increased follicle stimulating hormone (FSH) and luteinizing hormone (LH), and lowered etradiol (E2) serum levels at a dose of 15 and 45 mg/kg in female rats. Ovarian lymphocytosis, vascular dilatation and congestion, inflammatory cell infiltration, and increase in apoptotic cells were found in ovary tissues in exposure groups. For male rats, the weights decreased gradually, the ratio of epididymis weight over body weight increased, the motility of rat sperm changed, and the levels of FSH and testosterone (T) diminished. Pathological results showed the shedding of epithelial cells of raw seminiferous tubule, disordered arrangement of cells in the tube, and the appearance of cell apoptosis and death in the exposure group. At the same time, Ni NPs resulted in a change of the Reproductive index and the offspring development of rats. Further research is needed to elucidate exposure to human populations and mechanism of actions.
Robert E. Chapin - One of the best experts on this subject based on the ideXlab platform.
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Alternative Models of Developmental and Reproductive Toxicity in Pharmaceutical Risk Assessment and the 3Rs.
ILAR journal, 2016Co-Authors: Kimberly C. Brannen, Robert E. Chapin, Abigail Jacobs, Maia L. GreenAbstract:In the pharmaceutical industry, preclinical developmental and Reproductive Toxicity studies are conducted in laboratory animals in order to predict and prevent adverse effects of drugs on human Reproductive health and development. However, these studies require a relatively large number of animals and are usually conducted late in the drug development process. Early, simple, and inexpensive screening assays could facilitate smarter decisions, reductions in animal use, and development of safe drugs. The current state and future needs for alternative models of developmental and Reproductive Toxicity are reviewed here. The most popular predictive developmental Toxicity assays are embryonic stem cells, rodent whole embryo culture, and zebrafish, each of which involves fairly well-developed techniques with demonstrated utility in drug discovery and development. In vitro or ex vivo methods for male and female Reproductive Toxicity are less established, but there are promising assays available or being developed that may be useful in drug development, especially for elucidating mechanisms or screening backup compounds. While a number of challenges remain, much progress has been made in alternative developmental and Reproductive Toxicity models to date, and there is a strong collective enthusiasm in the industry to continue moving them forward. Therefore, it appears that these approaches may be widely used in the near future.
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More than just hormones: H295R cells as predictors of Reproductive Toxicity.
Reproductive toxicology (Elmsford N.Y.), 2014Co-Authors: Jodi M. Maglich, Robert E. Chapin, Max Kuhn, Mathew T. PletcherAbstract:Many 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, 3βHSD2, 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.
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Reproductive Toxicity of di n butylphthalate in a continuous breeding protocol in sprague dawley rats
Environmental Health Perspectives, 1997Co-Authors: Robert N Wine, Leta H Barnes, Dushyant K Gulati, Robert E. ChapinAbstract:The phthalate ester di-n-butylphthalate (DBP) is used extensively in the manufacture of plastics; its Reproductive Toxicity was tested in rats by the National Toxicology Program's Reproductive Asse...
Olivier Geffard - One of the best experts on this subject based on the ideXlab platform.
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Ovarian cycle and embryonic development in Gammarus fossarum: Application for Reproductive Toxicity assessment
Environmental Toxicology and Chemistry, 2010Co-Authors: Olivier Geffard, Benoît Xuereb, Arnaud Chaumot, Alain Geffard, Sylvie Biagianti, Claire Noel, Khedidja Abbaci, Jeanne Garric, Guy Charmantier, Mireille Charmantier-dauresAbstract:Among freshwater invertebrates, Gammarus fossarum is an important test organism and is currently used in ecotoxicology for acute and chronic assays; nevertheless, Reproductive Toxicity test methods are not yet available for these species. In the present study, the Reproductive cycle in Gammarus fossarum was characterized in order to propose a Reproductive Toxicity test encompassing molting, follicle growth, and embryonic development that will provide a better understanding of the mode of action of chemicals disrupting these hormone-regulated processes. A detailed description of the Reproductive cycle in Gammarus fossarum was obtained. As in some amphipods, molt and Reproductive cycles of G. fossarum females occur concurrently, lasting 30 d at 128C. Each molt stage is characterized by a specific marsupial embryonic development stage and the size of developing follicles visible on the ovarian membrane. Based on these results, a 21-d Reproductive Toxicity test is proposed for this species. This new bioassay was applied to identify the specific impact of different stressors: cadmium, methomyl, nonylphenol, and a starvation diet. Good reproducibility was obtained for different endpoints under control conditions and throughout the experiments. Preliminary robust reference values or benchmarks were proposed for these endpoints. Cadmium was found to specially inhibit secondary vitellogenesis. Nonylphenol had a specific concentration- dependent effect on embryonic development, with an increase in the percent abnormality from a concentration of 0.05 mg/L. A restricted food diet led to a significant delay in the molt cycle, which in turn induced inhibition of secondary vitellogenesis.
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ovarian cycle and embryonic development in gammarus fossarum application for Reproductive Toxicity assessment
Environmental Toxicology and Chemistry, 2010Co-Authors: Olivier Geffard, Benoît Xuereb, Arnaud Chaumot, Alain Geffard, Sylvie Biagianti, Claire Noel, Khedidja Abbaci, Jeanne Garric, Guy Charmantier, Mireille CharmantierdauresAbstract:Among freshwater invertebrates, Gammarus fossarum is an important test organism and is currently used in ecotoxicology for acute and chronic assays; nevertheless, Reproductive Toxicity test methods are not yet available for these species. In the present study, the Reproductive cycle in Gammarus fossarum was characterized in order to propose a Reproductive Toxicity test encompassing molting, follicle growth, and embryonic development that will provide a better understanding of the mode of action of chemicals disrupting these hormone-regulated processes. A detailed description of the Reproductive cycle in Gammarus fossarum was obtained. As in some amphipods, molt and Reproductive cycles of G. fossarum females occur concurrently, lasting 30 d at 12°C. Each molt stage is characterized by a specific marsupial embryonic development stage and the size of developing follicles visible on the ovarian membrane. Based on these results, a 21-d Reproductive Toxicity test is proposed for this species. This new bioassay was applied to identify the specific impact of different stressors: cadmium, methomyl, nonylphenol, and a starvation diet. Good reproducibility was obtained for different endpoints under control conditions and throughout the experiments. Preliminary robust reference values or benchmarks were proposed for these endpoints. Cadmium was found to specially inhibit secondary vitellogenesis. Nonylphenol had a specific concentration-dependent effect on embryonic development, with an increase in the percent abnormality from a concentration of 0.05 µg/L. A restricted food diet led to a significant delay in the molt cycle, which in turn induced inhibition of secondary vitellogenesis. Environ. Toxicol. Chem. 2010;29:2249–2259. © 2010 SETAC
Moa Kvarnryd - One of the best experts on this subject based on the ideXlab platform.
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Xenopus tropicalis as a test system for developmental and Reproductive Toxicity.
Journal of toxicology and environmental health. Part A, 2009Co-Authors: Cecilia Berg, Irina Gyllenhammar, Moa KvarnrydAbstract:The usefulness of Xenopus tropicalis as a model species to investigate endocrine disruption and developmental Reproductive Toxicity was assessed. In our test system tadpoles were exposed to test ...