Publications (16)34.94 Total impact
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Article: Exposure to diesel exhaust during fetal period affects behavior and neurotransmitters in male offspring mice.
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ABSTRACT: Exposure to ambient particulate matter (PM) has been associated with the onset of cardiovascular and respiratory diseases. Diesel exhaust particles (DEP) are major components of ambient PM. We first reported DEP in the central nervous system of offspring utilizing maternal inhalation to diesel exhaust (DE). In addition, we found that the effects of maternal exposure to DE reduced spontaneous motor activity. However, it is still unknown whether maternal exposure to DE affects higher order behavioral function. Therefore, the aim of the present study was to examine the effects of fetal exposure to DE on motor coordination, impulsive behavior and monoaminergic systems in various brain regions. The results of the rotating rod test showed that DE-exposed mice displayed decreased time on the rota rod compared to control mice. However, no changes were detected between the two groups in the hanging test. Furthermore, the cliff avoidance test revealed that DE-exposed mice spent more time in the corner and fell off an inverted glass beaker compared to control mice. High performance liquid chromatography analysis revealed that noradrenaline turnover in the cerebellum was decreased by prenatal exposure to DE, and was significantly increased in the hypothalamus. Dopamine and serotonin levels in various brain regions were also changed by prenatal exposure to DE. Our study found that prenatal exposure to DE alters motor coordination, impulsive behavior and related monoamine levels. Therefore, the present study underscores the role of behavioral changes related to monoamine in response to maternal inhalation of DE.The Journal of Toxicological Sciences 01/2013; 38(1):13-23. · 1.52 Impact Factor -
Article: Expression Profile of Extracellular Matrix and Adhesion Molecules in the Development of Endometriosis in a Mouse Model.
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ABSTRACT: Ectopic endometrial tissue induces various reactions in surrounding tissues, such as the surface of the ovary and peritoneal cavity, leading to endometriosis. The aim of this study is to investigate the expression profile of extracellular matrix (ECM) and adhesion molecules in the early steps of development of experimental mouse endometriosis, specifically in peritoneum adjacent to endometrium transplants attached via autotransplantation. The endometriosis model was induced by autotransplantation of endometrium to peritoneal tissue. Peritoneal tissues adjacent to the transplant were obtained at 1, 4, and 7 days posttransplantation. The results showed that messenger RNA expression levels of most of the integrins, collagens, and other ECM reached a peak at 7 days posttransplantation. Uniquely, Lamc2 was significantly increased to its maximum level within 24 hours posttransplantation and may be strongly associated with initiation of the development of endometriosis. These data will be helpful in further investigations of the treatment of endometriosis.Reproductive sciences (Thousand Oaks, Calif.) 08/2012; · 2.31 Impact Factor -
Article: Evaluation of the testicular toxicity of prenatal exposure to bisphenol A based on microarray analysis combined with MeSH annotation.
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ABSTRACT: Bisphenol A (BPA) is known to be an endocrine disruptor that affects the development of reproductive system. The aim of the present study was to investigate a group of testicular genes dysregulated by prenatal exposure to BPA. Pregnant ICR mice were treated with BPA by subcutaneous administration on days 7 and 14 of pregnancy. Tissue and blood samples were collected from 6-week-old male offspring. Testes were subjected to gene expression analysis using a testis-specific microarray (Testis2), consisting of 2,482 mouse cDNA clones annotated with Medical Subject Headings (MeSH) terms indicative of testicular components and functions. To interpret the microarray data, we used the MeSH terms significantly associated with the altered genes. As a result, MeSH terms related to androgens and Sertoli cells were extracted in BPA-treated groups. Among the genes related to Sertoli cells, downregulation of Msi1h, Ncoa1, Nid1, Hspb2, and Gata6 were detected in the testis of mice treated with BPA (twice administered 50 mg/kg). The MeSH terms associated with this group of genes may provide useful means to interpret the testicular toxicity of BPA. This article concludes that prenatal BPA exposure downregulates expression of genes associated with Sertoli cell function and affects the reproductive function of male offspring. Additionally, a method using MeSH to extract a group of genes was useful for predicting the testicular and reproductive toxicity of prenatal BPA exposure.The Journal of Toxicological Sciences 01/2012; 37(3):539-48. · 1.52 Impact Factor -
Article: Effect of fetal exposure to titanium dioxide nanoparticle on brain development - brain region information.
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ABSTRACT: The production of man-made nanoparticles is increasing in nanotechnology, and health effect of nanomaterials is of concern. We previously reported that fetal exposure to titanium dioxide (TiO(2)) affects the brain of offspring during the perinatal period. The aim of this study was to extract candidate brain regions of interest using a specific group of Medical Subject Headings (MeSH) from a microarray dataset of the whole brain of mice prenatally exposed to TiO(2) nanoparticle. After subcutaneous injection of TiO(2) (total 0.4 mg) into pregnant mice on gestational days 6-15, brain tissues were collected from male fetuses on embryonic day 16 and from male pups on postnatal days 2, 7, 14 and 21. Gene expression changes were determined by microarray and analyzed with MeSH indicating brain regions. As a result, a total of twenty-one MeSH were significantly enriched from gene expression data. The results provide data to support the hypothesis that prenatal TiO(2) exposure results in alteration to the cerebral cortex, olfactory bulb and some regions intimately related to dopamine systems of offspring mice. The genes associated with the striatum were differentially expressed during the perinatal period, and those associated with the regions related to dopamine neuron system and the prefrontal region were dysregulated in the later infantile period. The anatomical information gave us clues as to the mechanisms that underlie alteration of cerebral gene expression and phenotypes induced by fetal TiO(2) exposure.The Journal of Toxicological Sciences 01/2012; 37(6):1247-52. · 1.52 Impact Factor -
Article: Evaluation of testicular toxicology of doxorubicin based on microarray analysis of testicular specific gene expression.
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ABSTRACT: Testicular toxicity of chemical substances has been generally assessed by sperm properties and histology. However, the methods can provide only a few information of the mechanism of the toxicity. The aim of this study is to show a method that can evaluate an overview of testicular toxic mechanisms using a tissue-specific microarray and classification of genes using Medical Subject Headings (MeSH). Male ICR mice (6 weeks old) were treated with doxorubicin hydrochloride (0, 0.1, 0.3 mg/kg/time, three times per week) by subcutaneous injection for 6 weeks (until 11 weeks old). Six weeks after the final administration, tissue and blood samples were obtained. Testes were subjected to gene expression analysis using quantitative RT-PCR and cDNA microarray (testis2). To interpret the microarray data, genes were classified using MeSH related to the functions of testis and sperm. Doxorubicin (both 0.1 and 0.3 mg/kg group) induced a decrease in sperm normal morphology and mortality, daily sperm production, and the number of Sertoli cells in the seminiferous tubules. Quantitative RT-PCR and microarray analysis showed dysregulation of mRNA expression levels of genes related to Sertoli cells, germ cells and spermatogenesis. Analysis of microarray data showed a significant enrichment of a total of ten MeSH categories including Spermatogenesis, Sertoli cells, Germ cells and Male infertility. This article concluded that analysis using testicular specific microarray combined with MeSH showed a more comprehensive overview of testicular toxic mechanisms than existing methods; i.e., examination of sperm properties and the histological examinations.The Journal of Toxicological Sciences 10/2011; 36(5):559-67. · 1.52 Impact Factor -
Article: Current research and prospects for health effects of nanoparticles on offspring
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ABSTRACT: Caution in handling ceramic nanoparticles is required by workers and consumers if they are to be used safely and profitably. The small size of nanoparticles can bestow high reactivity and unique translocational properties. Studies have shown that exposure to some types of nanoparticles affects the respiratory, cardiovascular and central nervous systems and various organs. When pregnant mice were exposed to nanoparticles, various organs of offspring are also affected. Our recent studies showed that prenatal exposure to nanoparticles (carbon black and titanium dioxide) causes long-term adverse effects on the reproductive, respiratory and central nervous systems of offspring. The effects of nanoparticles on fetuses and children and the possibility of them leading to the onset of diseases in adulthood are of concern. Thus, it is important to research the risk of unintentional exposure to nanoparticles, including ceramic nanoparticles, from the environment and to attempt to identify methods to protect against their toxicity.IOP Conference Series Materials Science and Engineering 07/2011; 18(23):232001. -
Article: Clarithromycin and telithromycin increases interleukin-10 expression in the rat endometriosis model.
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ABSTRACT: Endometriosis is a common gynecological disorder associated with infertility. However, treatment options remain limited at present. Since the pathogenesis involves immune responses, the immunomodulatory effect of macrolide on endometriosis has been the focus of much research. A previous study showed that clarithromycin decreased stromal proliferation and promoted apoptosis of fibroblasts in an endometriosis model in rats; however, the mechanism of the effect remains unknown. The aim of this study is to investigate the effect of clarithromycin, one of the major macrolides, and telithromycin, one of the antibiotics belonging to a macrolide group (ketolide), on IL6, IL10 and Ccl2 expression in a rat endometriosis model induced by the surgical transplantation of endometrium onto the peritoneum in 8-week-old female Sprague-Dawley rats. After autotransplantation, the rats were given daily administration of clarithromycin (16 mg/kg/day or telithromycin (12 mg/kg/day) for 3 days. The induced lesions were examined 4 days after autotransplantation. After treatment, IL10 expression in the lesions was increased in rats treated with clarithromycin (1.70-fold) and telithromycin (2.88-fold). The drugs attenuated proliferative stromal lesion of the endometriosis model. The results showed that in the endometriosis model, the drugs enhanced expression of IL10, which may play a role in inhibiting excess inflammatory reaction with its therapeutic effect on the lesion. Macrolide and ketolide therapy may have significant value for the treatment of human endometriosis.Cytokine 06/2011; 55(3):339-42. · 3.02 Impact Factor -
Article: [Health effects of nanomaterials on next generation].
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ABSTRACT: In order to discuss the health effects of nanomaterials, we cannot disregard the research on the health effects of airborne particulates. It is said that many of the fine or ultrafine particles in airborne particulates originate from diesel vehicles in metropolitan areas. The results of not only animal experiments but many epidemiologic surveys and volunteer intervention experiments in humans are reported on the health effects of particles. Although the health effects of the particulate matter particle sizes below 10 µm (PM10) were investigated in the initial studies, recently even smaller particles have come to be regarded as questionable and research of the health effects of the minute particulate matter below 2.5 µm (PM2.5) has been done. However, our recent study about maternal exposure to diesel exhaust suggests that health effect study of PM0.1, particles below 0.1 µm (100 nm), namely nanoparticles, is necessary from now on. We are proceeding with the study of the health effects of various types of intentionally produced nanomaterials such as carbon black, carbon nanotube, fullerene and titanium dioxide, examining in particular their influence on next generation. Although there are differences in the sites affected and the seriousness of the damage, basically similar findings to DEPs mentioned above are being discovered in research on nanomaterials. Regardless of dosage and administration method, such as inhalation, endotracheal administration, nasal drip and subcutaneous administration, once nanomaterials enter the bloodstream of a pregnant mother mouse, they move to the offspring and have effects on them. The effects may appear as various symptoms in the process of growth after birth, and can sometimes lead to the onset and aggravation of serious diseases.Yakugaku zasshi journal of the Pharmaceutical Society of Japan 02/2011; 131(2):229-36. · 0.39 Impact Factor -
Conference Proceeding: A Novel Analysis Tool to Interpret Microarray Results Using Multiple Gene Annotation.
Proceedings of the ISCA 3rd International Conference on Bioinformatics and Computational Biology, BICoB-2011, March 23-25, 2011, Holiday Inn Downtown-Superdome, New Orleans, Louisiana, USA; 01/2011 -
Article: Pathological study for the effects of in utero and postnatal exposure to diesel exhaust on a rat endometriosis model.
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ABSTRACT: Previous studies have shown that prenatal and postnatal exposure to diesel exhaust (DE), which is known to be one of the main constituents of air pollution, enhances the persistence of endometriosis in a rat model. The aim of this study is to investigate the pathological changes induced by DE exposure in a rat model of endometriosis. Pregnant Sprague-Dawley rats were exposed to DE or clean air beginning on gestational day 2 and neonatal rats were persistently exposed to DE or clean air. Endometriosis was induced by autotransplantation of endometrium onto the peritoneum of eight-week-old female offspring. Endometriotic lesions were examined at 7 and 14 days post-transplantation. As a result, infiltration of activated mast cells remained in deeper area of peritoneal tissue around the endometriosis model compared to the control group at 14 days post-autotransplantation. In the DE exposure group, 14 days post-transplant, the remaining lesions contained fibroblasts and activated mast cells, which were surrounded by collagen fibers. The data showed that prenatal and postnatal DE exposure enhances the activation of mast cells and prolongs the persistence of collagen fibers in the induced rat model of endometriosis.The Journal of Toxicological Sciences 01/2011; 36(4):493-8. · 1.52 Impact Factor -
Article: Maternal exposure to carbon black nanoparticle increases collagen type VIII expression in the kidney of offspring.
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ABSTRACT: The potential health risks of inhaling nanomaterials are of great concern because of their high specific activity and their unique property of translocation. Earlier studies showed that exposure to nanoparticles through the airway affects both respiratory and extrapulmonary organs. When pregnant mice were exposed to nanoparticles, the respiratory system, the central nervous system and the reproductive system of their offspring were affected. The aim of this study was to assess the effect of maternal exposure to nanoparticles on the offspring, particularly on the kidney. Pregnant ICR mice were exposed to a total of 100 µg of carbon black nanoparticle on the fifth and the ninth days of pregnancy. Samples of blood and kidney tissue were collected from 3-week-old and 12-week-old male offspring mice. Collagen expression was examined by quantitative RT-PCR and immunohistochemistry. Serum levels of creatinine and blood urea nitrogen were examined. Exposure of pregnant ICR mice to carbon black resulted in increased expression of Collagen, type VIII, a1 (Col8a1) in the tubular cells in the kidney of 12-week-old offspring mice but not in 3-week-old ones. The levels of serum creatinine and blood urea nitrogen, indices of renal function, were not different between the groups. These observations were similar to those of tubulointerstitial fibrosis in diabetic nephropathy. These results suggest that maternal exposure to carbon black nanoparticle induces renal abnormalities similar to tubulointerstitial fibrosis in diabetic nephropathy are induced in the kidney of offspring.The Journal of Toxicological Sciences 01/2011; 36(4):461-8. · 1.52 Impact Factor -
Article: In utero exposure to a low concentration of diesel exhaust affects spontaneous locomotor activity and monoaminergic system in male mice.
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ABSTRACT: Epidemiological studies have suggested that suspended particulate matter (SPM) causes detrimental health effects such as respiratory and cardiovascular diseases, and that diesel exhaust particles from automobiles is a major contributor to SPM. It has been reported that neonatal and adult exposure to diesel exhaust damages the central nervous system (CNS) and induces behavioral alteration. Recently, we have focused on the effects of prenatal exposure to diesel exhaust on the CNS. In this study, we examined the effects of prenatal exposure to low concentration of diesel exhaust on behaviour and the monoaminergic neuron system. Spontaneous locomotor activity (SLA) and monoamine levels in the CNS were assessed. Mice were exposed prenatally to a low concentration of diesel exhaust (171 microg DEP/m(3)) for 8 hours/day on gestational days 2-16. SLA was assessed for 3 days in 4-week-old mice by analysis of the release of temperature-associated infrared rays. At 5 weeks of age, the mice were sacrificed and the brains were used for analysis by high-performance liquid chromatography (HPLC). Mice exposed to a low concentration of diesel exhaust showed decreased SLA in the first 60 minutes of exposure. Over the entire test period, the mice exposed prenatally to diesel exhaust showed decreased daily SLA compared to that in control mice, and the SLA in each 3 hour period was decreased when the lights were turned on. Neurotransmitter levels, including dopamine and noradrenaline, were increased in the prefrontal cortex (PFC) in the exposure group compared to the control group. The metabolites of dopamine and noradrenaline also increased in the PFC. Neurotransmitter turnover, an index of neuronal activity, of dopamine and noradrenaline was decreased in various regions of the CNS, including the striatum, in the exposure group. The serum corticosterone level was not different between groups. The data suggest that decreased SLA in mice exposed prenatally to diesel exhaust is due to facilitated release of dopamine in the PFC. These results indicate that exposure of mice in utero to a low concentration of diesel exhaust decreases SLA and alters the neurochemical monoamine metabolism of several regions of the brain.Particle and Fibre Toxicology 03/2010; 7:7. · 7.25 Impact Factor -
Article: Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse.
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ABSTRACT: Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information. Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system.Particle and Fibre Toxicology 08/2009; 6:20. · 7.25 Impact Factor -
Article: Microarray analysis provides insight into the early steps of pathophysiology of mouse endometriosis model induced by autotransplantation of endometrium.
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ABSTRACT: To characterize the biochemical alterations that occur in the peritoneal tissue of the mouse endometriosis model during early development of the lesion using microarray analysis. The endometriosis model was induced by autotransplantation of endometrium in 8-week-old female ICR mice. Peritoneum only (excluding the transplant) was obtained 24, 48, and 96 h after the autotransplantation and subjected to microarray analysis. To interpret the large amounts of data generated and to enable a functional analysis, genes were classified using Gene Ontology (GO) and Medical Subject Heading (MeSH) terms, and the results were compared with previous reports on endometriosis. Of the upregulated genes, those involved in the inflammatory response, cell adhesion, extracellular matrix, wound healing, hormones, and leukocytes were significantly enriched 24 and 48 h after autotransplantation. Those of cytokines, antibody-producing cells, dendritic cells, inflammation, and infertility were enriched after 96 h. Analysis using GO and MeSH provided different information. Particularly, MeSH showed a link between an anatomical and diseased phenotype with common genes found to be upregulated. The factors occurring during early development of endometriosis induced by endometrium autotransplantation are increase in adhesion molecules and inflammatory responses rather than angiogenesis. Data presented herein may reveal a novel therapeutic gene targets and will contribute to knowledge for the treatment of this currently incurable disease.Life sciences 05/2009; 84(23-24):832-7. · 2.56 Impact Factor -
Article: Early development origins of adult disease caused by malnutrition and environmental chemical substances
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ABSTRACT: We observed that maternal exposure to diesel exhaust (DE) and diesel exhaust particles (DEPs) damaged the reproductive and central nervous systems in mice and rats. These observations suggest that impairment of early development induced by maternal exposure to DE and DEP causes several disorders after growing up. To eluci-date the effects of maternal exposure to environmental substances, we review here a hypothesis of fetal and early developmental origins of adult disease. Recent studies influenced by Dr. Barker's Thrifty Phenotype Hypothe-sis have led to advances in understanding how fetal and infant malnutrition can permanently and adversely alter the development of tissues and organs. Several epidemiological surveys in humans have uncovered links between maternal malnutrition and effects on the organs such as the kidney, pancreas, liver, muscles, adipocytes, and the hypothalamic-pituitary-adrenal (HPA) axis. These observations were examples of critical period programming. The idea has been applied to examining possible fetal and early origins of other diseases. Interestingly, many reports showed that similar phenomena were induced by perinatal exposure to airborne environmental pollutants. Studies have shown that maternal DE exposure disrupts reproductive development and damages the central nervous sys-tem. In addition, perinatal exposure to tobacco smoke has been linked to several respiratory disorders. These results show that early development is a critical determinant of adult physiology and much care should be taken to ensure the proper environment for fetal development. This idea is especially topical currently, where rapid industrialization in Asia has accelerated changes in environment and increased pollution.Journal of Health Science. 01/2009; 55:11-19. -
Article: Cytokine and chemokine expression in a rat endometriosis is similar to that in human endometriosis.
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ABSTRACT: The pathogenesis of endometriosis, a gynecologic disorder associated with infertility, appears to involve immune responses. However, the details involved have not been clarified. In this study, we analyzed expression levels of interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1, eosinophil chemotactic protein, macrophage inflammatory protein-1alpha, and regulated on activation normal T cell expressed and secreted (RANTES) and CC chemokine receptor 1 in endometriotic lesions in a rat model in which endometrium is autotransplanted onto peritoneal tissue and found that they were remarkably increased, while those of IL-2, IL-4, and interferon-gamma were not. These results were obtained in a rat model induced by autologous, not allogeneic, transplantation of endometrial epithelium to the peritoneum. Expression of these factors is consistent with that of endometriosis in humans. Therefore, this model may be useful in the investigation of the pathogenesis and treatment of endometriosis.Cytokine 07/2008; 43(2):105-9. · 3.02 Impact Factor
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Institutions
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2009–2013
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Tokyo University of Science
- • Department of Pharmaceutical Sciences
- • Research Institute for Science and Technology
Tokyo, Tokyo-to, Japan
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