Jun Yoshinaga

The University of Tokyo, Tōkyō, Japan

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Publications (143)294.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: During a cross-validation practice of urinary analysis of pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) by two laboratories (Lab A and Lab B), difference in 3-PBA concentration was noticed. The analytical methods used in the exercise were enzymatic deconjugation (glucuronidase/sulfatase) followed by solid phase extraction and isotope dilution LC-MS-MS determination (Lab A) and acidic deconjugation followed by liquid-liquid extraction and gas chromatography-mass spectrometry determination (Lab B). A significant difference was found for one of the five samples: lower value was obtained in Lab A. Use of acidic deconjugation in Lab A resulted in comparable value with the analytical result for this sample originally obtained in Lab B. The comparison was extended to 42 urine samples taken from Japanese males in Lab A by using the two different deconjugation methods and LC-MS-MS determination. Significantly lower value was obtained for enzymatic deconjugation in some of the 42 urine samples. The results suggested the presence of other conjugated species of 3-PBA than glucuronide and sulfate in human urine. Although the overall agreement between the values obtained by the deconjugation methods was fair, it appears that urine samples should be pretreated by acidic deconjugation for the analysis in biological monitoring of pyrethroid exposure. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Journal of analytical toxicology 12/2014; 39(2). DOI:10.1093/jat/bku142 · 2.63 Impact Factor
  • Yayoi Suzuki, Aya Hisada, Jun Yoshinaga
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    ABSTRACT: Objective: To evaluate the representativeness of single measurement of urinary soy-isoflavone concentrations for the assessment of long-term intake levels. Methods: Five urine samples taken from 14 Japanese female subjects over 2–3 months were measured for daidzein and equol by gas chromatography-mass spectrometry (GC-MS). Results: Geometric mean daidzein and equol concentrations of 14 subjects were 582 and 2.66 μg/g creatinine, respectively. Intra-class correlation coefficients for daidzein and equol were 0.355 (95% CI: 0.130–0.649) and 0.741 (0.551–0.891), respectively. Conclusion: Single measurement of urinary equol is effective for the assessment of long-term equol status of Japanese subject while that of daidzein is not.
    Biomarkers 05/2014; DOI:10.3109/1354750X.2014.922619 · 2.52 Impact Factor
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    ABSTRACT: Pyrethroid insecticides have been shown to possess thyroid hormone disrupting properties in previous animal studies. In this study, the relationship between maternal exposure to pyrethroid insecticides during pregnancy and neonatal thyroid hormone status (free thyroxine (fT4) and thyroid stimulating hormone (TSH) in whole blood) and birth sizes were explored in 147 mother-neonate pairs in Tokyo. The concentration of 3-phenoxybenzoic acid (3-PBA) in maternal urine, sampled in the first trimester of gestation, was used for pyrethroid exposure assessment. Neonatal fT4 and TSH were within the normal range except for one elevated TSH (but normal fT4) in a neonate. Multiple regression analyses with stepwise variable selection did not extract maternal 3-PBA as significant for neonatal fT4 and TSH, indicating that maternal pyrethroid exposure had no apparent effect on the neonatal thyroid hormone status of the neonate subjects. For birth weight and head circumference, maternal 3-PBA was selected as significant with a positive partial regression coefficient along with other factors known to increase birth sizes of neonates (gestational weeks or maternal BMI). It was not clear if this was causal because no biological mechanism was apparent.
    Science of The Total Environment 05/2014; 488-489C:275-279. DOI:10.1016/j.scitotenv.2014.04.104 · 4.10 Impact Factor
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    ABSTRACT: The levels of 25 elements in house dust collected from 100 general Japanese residences were measured. Factor analysis was applied on the multi-element data to explore source of Pb (median concentration 49.1 mg/kg) in house dust. Six factors were extracted and Pb was found to have great loading on the fifth factor with Sb and Sn, suggesting solder (Sn), and plastic and metals (Sb) may be the sources of Pb in the house dust of Japanese residences. No significant loading was found on soil-related factors indicating non-significant contribution of Pb in track-in soil. Seven heavy metals (Cd, Cu, Mo, Pb, Sb, Sn, and Zn) were found in house dust at >10 times more condensed than crustal abundance. Health risk of these elements to children via the ingestion of house dust was estimated based on the comparison with tolerable daily intake and found to be non-significant for most of the elements.
    Environmental Pollution 03/2014; 189C:223-228. DOI:10.1016/j.envpol.2014.03.003 · 3.90 Impact Factor
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    ABSTRACT: The associations between serum levels of reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, sex hormone-binding globulin, inhibin B and calculated free testosterone) and urinary metabolite concentration of pyrethroid insecticides [3-phenoxybenzoic acid (3-PBA)] were explored in 322 male university students in suburban Tokyo. The subjects constituted part of a large cross-sectional survey on the reference value of semen quality of Japanese men. Urinary 3-PBA was detectable in 91% of the subjects demonstrating ubiquitous exposure among the general population. However, there were no associations between urinary 3-PBA and serum hormone levels. This result was inconsistent with those reported in China and the USA for subjects who had similar levels of urinary 3-PBA to the present subjects. One of the possible reasons of the inconsistency might be different composition of pyrethroid insecticides to which the subjects were exposed; 3-PBA is a common metabolite of a number of pyrethroids and thus lacks specificity to compounds that may have different potentials of reproductive toxicity. Another reason might be related to the fact that our subjects were university students who were not aware of their own fertility, whereas the previous study subjects were infertility patients. However, the multiple regression models could explain only a limited fraction of total variance in serum levels of hormones. Identification of other contributors is warranted.
    Andrology 03/2014; 2(3). DOI:10.1111/j.2047-2927.2014.00202.x · 3.37 Impact Factor
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    ABSTRACT: Pyrethroid insecticides have been shown to possess thyroid hormone disrupting properties in previous animal studies. In this study, the relationship between maternal exposure to pyrethroid insecticides during pregnancy and neonatal thyroid hormone status (free thyroxine (fT4) and thyroid stimulating hormone (TSH) in whole blood) and birth sizes were explored in 147 mother–neonate pairs in Tokyo. The concentration of 3-phenoxybenzoic acid (3-PBA) in maternal urine, sampled in the first trimester of gestation, was used for pyrethroid exposure assessment. Neonatal fT4 and TSH were within the normal range except for one elevated TSH (but normal fT4) in a neonate. Multiple regression analyses with stepwise variable selection did not extract maternal 3-PBA as significant for neonatal fT4 and TSH, indicating that maternal pyrethroid exposure had no apparent effect on the neonatal thyroid hormone status of the neonate subjects. For birth weight and head circumference, maternal 3-PBA was selected as significant with a positive partial regression coefficient along with other factors known to increase birth sizes of neonates (gestational weeks or maternal BMI). It was not clear if this was causal because no biological mechanism was apparent.
    Science of The Total Environment 01/2014; s 488–489:275–279. · 4.10 Impact Factor
  • Tomoko Oguri, Jun Yoshinaga
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    ABSTRACT: The objective was to estimate the inorganic arsenic (iAs) intake of the general Japanese adult population by a probabilistic approach.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2014; 69(3):177-86. DOI:10.1265/jjh.69.177
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    ABSTRACT: The levels of 25 elements in house dust collected from 100 general Japanese residences were measured. Factor analysis was applied on the multi-element data to explore source of Pb (median concentration 49.1 mg/kg) in house dust. Six factors were extracted and Pb was found to have great loading on the fifth factor with Sb and Sn, suggesting solder (Sn), and plastic and metals (Sb) may be the sources of Pb in the house dust of Japanese residences. No significant loading was found on soil-related factors indicating non-significant contribution of Pb in track-in soil. Seven heavy metals (Cd, Cu, Mo, Pb, Sb, Sn, and Zn) were found in house dust at >10 times more condensed than crustal abundance. Health risk of these elements to children via the ingestion of house dust was estimated based on the comparison with tolerable daily intake and found to be non-significant for most of the elements.
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    ABSTRACT: The purpose of this study was to investigate possible associations between concentrations of hydroxylated PCBs (OH-PCBs) and PCBs in the serum of women in the first trimester of pregnancy and thyroid hormone levels and body size of newborn infants in 79 mother-neonate pairs. We measured 16 OH-PCB isomers and 29 PCB isomers in the serum of Japanese women sampled at 11.1±1.9 weeks of gestation. The concentrations of free thyroxine (fT4) and thyroid stimulating hormone (TSH) were measured in whole blood spots on filter papers sampled from the neonates. Dietary and lifestyle information of the mothers were obtained by self-administered questionnaires. Geometric mean (GM) concentrations of the sum of 16 OH-PCB isomers and of 29 PCB isomers were 1.2×10(2)pg/g wet wt. and 69ng/g lipid wt., respectively, in maternal serum. The GM concentrations of neonatal fT4 and TSH were 2.21ng/dL and 1.37μIU/mL, respectively. Multiple regression analysis was performed using measures of neonatal thyroid hormones as dependent variable and serum levels of OH-PCBs/PCBs and other potential covariates (age, pre-pregnancy weight, smoking status, etc.) as independent variables. The results demonstrated a significant positive association between the concentrations of some OH-PCB isomers and that of neonatal TSH. There were no significant associations between levels of PCBs and neonatal fT4, or between OH-PCBs/PCBs and body size of neonates. We conclude that exposure to/body burden of OH-PCBs, but not PCBs, at environmental levels during the first trimester of pregnancy can affect neonatal thyroid hormone status.
    International journal of hygiene and environmental health 11/2013; DOI:10.1016/j.ijheh.2013.10.004 · 3.28 Impact Factor
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    ABSTRACT: The present study aimed at assessing the relationship between exposure to pyrethroid insecticides and semen quality in 323 university students recruited in a population-based manner in Metropolitan Tokyo. Urinary concentrations of pyrethroid insecticide metabolite, 3-phenoxybenzoic acid (3-PBA), were measured by LC/MS/MS and semen parameters were measured by following internationally harmonized protocols. Median urinary 3-PBA concentration was 0.641ng/mL (specific gravity-adjusted, n=322). Median values of semen volume, sperm concentration, motility, total number of sperm, and total number of motile sperm were 2.5mL, 56×10(6)/mL, 61%, 141×10(6), and 82×10(6), respectively. Urinary concentration of 3-PBA was not selected as significant in multiple regression models indicating, in contrast to previous findings, that environmental exposure to pyrethroid insecticides did not affect semen quality. This inconsistency may be related to exposure to different pyrethroid insecticides and/or levels of exposure as well as to survey design (hospital-vs population-based subject recruitment).
    Reproductive Toxicology 11/2013; DOI:10.1016/j.reprotox.2013.10.010 · 2.77 Impact Factor
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    ABSTRACT: Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10-12 gestational weeks recruited at a university hospital in Tokyo during 2009-2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06)μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83-3.41ng/dL, 0.01-27.4μIU/mL and 16.4-54.4μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected.
    Environmental Research 10/2013; 127. DOI:10.1016/j.envres.2013.10.001 · 3.95 Impact Factor
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    ABSTRACT: The concentrations of arsenic (As) species in 19 food composites prepared from 159 food items purchased in Shizuoka city, Japan, were determined (1) to estimate total daily intake of inorganic As (InAs) and some organic As species and (2) to determine food contributing to total daily InAs intake. As analysis included extraction of As species with a synthetic gastric juice (0.07 mol/L HCl + 0.01 % pepsin) from food composite and high-performance liquid chromatography-high efficiency photo-oxidation-hydride generation-inductively coupled plasma mass spectrometry. InAs was detected in 9 of 19 food composites at a concentration of 0.423-450 ng As/g fresh-weight. Daily intake of InAs from cereals was greatest (13 μg/person/day) followed by algae (5.7 μg/person/day), and the intake from the two categories constituted 90 % of the total daily InAs intake of adults (21 μg/person/day on a bioaccessible-fraction basis and 24 μg/person/day on a content basis). Analysis of individual food items showed that rice and hijiki contributed virtually 100 % of InAs from cereals and algae, respectively. The present survey indicated that InAs from rice and hijiki consumption contributed to total daily InAs intake and consequently to significant cancer risk of the general Japanese population. Daily intake of some organic forms of As and their contributing food categories was also estimated.
    Archives of Environmental Contamination and Toxicology 08/2013; DOI:10.1007/s00244-013-9947-8 · 1.96 Impact Factor
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  • Tomoko Oguri, Yuri Ishibashi, Jun Yoshinaga
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    ABSTRACT: Total and inorganic arsenic (tAs and iAs) analysis of soils and house dust samples, collected pair-wise from 41 residences of general public in Japan, was carried out to estimate contributions of these non-dietary oral sources to total daily exposure level of iAs, an established human carcinogen. Total As concentration in the samples was determined after mixed acid digestion followed by ICP mass spectrometric (ICPMS) determination. Non-spectroscopic interference arising from residual carbon in the digest was successfully compensated by addition of 3% acetic acid to sample digest and standard solution. Concentration of iAs in soil and house dust samples (n=20 each) was measured by liquid chromatography- ICPMS after extraction with synthetic gastric juice. Median tAs concentration in soil (n=38) and house dust (n=40) was 10 and 2.5 mg/kg, respectively. Median iAs (AsIII+AsV) concentration was <0.01 and 0.24 mg/kg, respectively. Assuming that adult unintentionally ingest 50 mg each of soil and house dust, daily exposure level was estimated to be 0.0005 and 0.012 μg/day, respectively. When recently reported daily dietary iAs intake (mean of two estimates: 15.4 μg/day) is considered, contributions from soil and house dust to total daily oral exposure was estimated to be 0.003 and 0.08%, respectively. Soil and house dust ingestion, as well as inhalation exposure (estimated to be 0.02 μg/day), was found to be insignificant for total daily iAs exposure of Japanese.
    01/2013; 23(1):43-47. DOI:10.5985/jec.23.43
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    ABSTRACT: Objectives: The lead content of excavated bone samples from archaeological sites in Hokkaido was measured to obtain insight into the source of human lead contamination known in the historic Japanese Edo era. Methods: Fifty-seven rib samples excavated from 11 sites of five different eras in Hokkaido were analyzed for lead (Pb), calcium (Ca), and iron (Fe) contents by ICP mass spectrometry and ICP emission spectrometry. Results: The Pb/Ca ratio (mg Pb/kg Ca) was low (approximately 2.0) and constant from the Jomon (approximately 5000 BP) to the Satsumon (approximately 750 BP) eras; however, its median increased to 11 in the Modern era. This elevation of Pb/Ca ratio in the bone samples from sites of the Modern era was not considered to be due to a greater bone contamination with soil particles because of similar Fe concentrations in the bone samples from this era to those in other eras. This historic trend of Pb/Ca ratio was similar to that observed in other parts of Japan. The elevated Pb/Ca ratio in the bone samples excavated from sites in the Modern era in other parts of Japan, that is, Edo era, has been ascribed to the usage of face powder containing Pb; however, people inhabiting Hokkaido in those days, the Ainu, were not considered to have the custom of using face powder. Conclusions: Contamination source(s) other than face powder was postulated in the Modern era of both Hokkaido and other parts of Japan.
    Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) 01/2013; 68(1):53-7. DOI:10.1265/jjh.68.53
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    ABSTRACT: We hypothesized that polymorphic differences among individuals might cause variations in the effect that environmental endocrine disruptors (EEDs) have on male genital malformations (MGMs). In this study, individual variation in the genetic response to low-dose bisphenol A (BPA) was investigated in human foreskin fibroblast cells (hFFCs) derived from child cryptorchidism (CO) and hypospadias (HS) patients. hFFCs were collected from control children without MGMs (n = 5) and child CO and HS patients (n = 8 and 21, respectively). BPA exposure (10 nM) was found to inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group (0.74-fold, P = 0.0034) but not in the control group (0.93-fold, P = 0.84) and CO group (0.94-fold, P = 0.70). Significantly lower levels of MMP11 expression were observed in the HS group compared with the control group (0.80-fold, P = 0.0088) and CO group (0.79-fold, P = 0.039) in response to 10 nM BPA. The effect of single-nucleotide polymorphism rs5000770 (G>A), located within the aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual sensitivity to low-dose BPA was investigated in the HS group. A significant difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA was observed between AA and AG/GG groups (n = 6 and 15, respectively. P = 0.031). However, no significant difference in ARNT2 expression was observed (P = 0.18). This study advances our understanding of the specificity of low-dose BPA effects on human reproductive health. Our results suggest that genetic variability among individuals affects susceptibility to the effects of EEDs exposure as a potential cause of HS.
    PLoS ONE 12/2012; 7(12):e52756. DOI:10.1371/journal.pone.0052756 · 3.53 Impact Factor
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    ABSTRACT: OBJECTIVES: The purpose of this study was to investigate the associations between serum concentrations of hydroxylated PCBs (OH-PCBs) and PCBs and measures of thyroid hormone status of Japanese pregnant women. METHODS: The concentrations of free thyroxine (fT4), thyroid stimulating hormone (TSH), and thyroxine binding globulin (TBG) as well as 16 OH-PCB isomers and 29 PCB isomers were analyzed in the serum of 129 women sampled in the first trimester of gestation. Dietary and lifestyle information of the subjects was obtained by self-administered questionnaire. Multiple regression analysis was performed using measures of thyroid hormones as the dependent variable and serum levels of OH-PCBs/PCBs, urinary iodine concentration, and other potential covariates (age, BMI, smoking, etc.) as independent variables. RESULTS: Geometric mean (GM) concentration of the sum of 16 isomers of OH-PCBs was 120 pg/g wet wt. and that of 29 isomers of PCBs was 68 ng/g lipid wt., respectively, in the serum of the subjects. Iodine nutrition was considered adequate to high from urinary iodine level (GM, 370 μg/g creatinine). The mean concentration of TSH, fT4 and TBG was 1.34 ± 1.37 μIU/mL, 1.22 ± 0.16 ng/dL and 33.0 ± 6.4 μg/mL, respectively, with a small number of subjects who were outside the reference range. Multiple regression analysis revealed that serum concentrations of OH-PCBs/PCBs were not significantly associated with any of the measures of thyroid hormone status. CONCLUSIONS: Exposure/body burden of OH-PCBs and PCBs at environmental levels does not have a measurable effect on thyroid hormones.
    Environmental Health and Preventive Medicine 09/2012; DOI:10.1007/s12199-012-0306-6
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    ABSTRACT: Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases.
    NeuroToxicology 09/2012; 33(5):1375-80. DOI:10.1016/j.neuro.2012.08.016 · 3.05 Impact Factor
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    ABSTRACT: Zinc (Zn) deficiency in utero has been shown to cause a variety of disease states in children in developing countries, which prompted us to formulate the hypothesis that fetal epigenetic alterations are induced by zinc deficiency in utero. Focusing on metallothionein (MT), a protein that contributes to Zn transport and homeostasis, we studied whether and how the prenatal Zn status affects gene expression. Pregnant mice were fed low-Zn (IU-LZ, 5.0 μg Zn/g) or control (IU-CZ, 35 μg Zn/g) diet ad libitum from gestation day 8 until delivery, with a regular diet thereafter. Bisulfite genomic sequencing for DNA methylation and chromatin immunoprecipitation assay for histone modifications were performed on the MT2 promoter region. We found that 5-week-old IU-LZ mice administered cadmium (Cd) (5.0 mg/kg b.w.) have an elevated abundance of MT2 mRNA compared with IU-CZ mice. Alteration of histone modifications in the MT2 promoter region having metal responsive elements (MREs) was observed in 1-day-old and 5-week-old IU-LZ mice compared with IU-CZ mice. In addition, prolongation of MTF1 binding to the MT2 promoter region in 5-week-old IU-LZ mice upon Cd exposure is considered to contribute to the enhanced MT2 induction. In conclusion, we found for the first time that Zn deficiency in utero induces fetal epigenetic alterations and that these changes are being stored as an epigenetic memory until adulthood.
    The Journal of nutritional biochemistry 08/2012; 24(1). DOI:10.1016/j.jnutbio.2012.05.013 · 4.59 Impact Factor
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    ABSTRACT: We have previously established a protocol for the neural differentiation of mouse embryonic stem cells (mESCs) as an efficient tool to evaluate the neurodevelopmental toxicity of environmental chemicals. Here, we described a multivariate bioinformatic approach to identify the stage-specific gene sets associated with neural differentiation of mESCs. We exposed mESCs (B6G-2 cells) to 10(-8) or 10(-7) M of retinoic acid (RA) for 4 days during embryoid body formation and then performed morphological analysis on day of differentiation (DoD) 8 and 36, or genomic microarray analysis on DoD 0, 2, 8, and 36. Three gene sets, namely a literature-based gene set (set 1), an analysis-based gene set (set 2) using self-organizing map and principal component analysis, and an enrichment gene set (set 3), were selected by the combined use of knowledge from literatures and gene information selected from the microarray data. A gene network analysis for each gene set was then performed using Bayesian statistics to identify stage-specific gene expression signatures in response to RA during mESC neural differentiation. Our results showed that RA significantly increased the size of neurosphere, neuronal cells, and glial cells on DoD 36. In addition, the gene network analysis showed that glial fibrillary acidic protein, a neural marker, remarkably up-regulates the other genes in gene set 1 and 3, and Gbx2, a neural development marker, significantly up-regulates the other genes in gene set 2 on DoD 36 in the presence of RA. These findings suggest that our protocol for identification of developmental stage-specific gene expression and interaction is a useful method for the screening of environmental chemical toxicity during neurodevelopmental periods.
    Frontiers in Genetics 08/2012; 3:141. DOI:10.3389/fgene.2012.00141

Publication Stats

2k Citations
294.13 Total Impact Points

Institutions

  • 1988–2014
    • The University of Tokyo
      • • Department of Natural Environmental Studies
      • • Graduate School of Frontier Sciences
      • • Department of International Health
      • • Department of Biophysics and Biochemistry
      Tōkyō, Japan
  • 1992–2001
    • National Institute for Environmental Studies
      • Center for Material Cycles and Waste Management Research
      Tsukuba, Ibaraki, Japan
  • 1990
    • National Institute for Minamata Disease
      Mizumata, Kumamoto, Japan