Researcher Database

Houman Goudarzi
Faculty of Medicine Center for Medical Education and International Relations
Assistant Professor

Researcher Profile and Settings

Affiliation

  • Faculty of Medicine Center for Medical Education and International Relations

Job Title

  • Assistant Professor

Degree

  • MD, PhD

Research funding number

  • 40713607

J-Global ID

Profile

  • I am a motivated, adaptable, and responsible hard worker with good communication skills who works effectively in a team and has the ability to meet deadlines. I am a medical doctor with PhD degree working as an Assistant Professor in Graduate School of Medicine, Hokkaido University. I am looking for a new challenge where I can use my existing skills and conduct further teaching activities and research to develop my career and scientific expertise.

Research Interests

  • Biomarkers   Public health   Medical Education   Epidemiology   Respiratory Medicine   Genetic Medicine   Childhood asthma   COPD   Allergy   Adulthood Asthma   

Research Areas

  • Life sciences / Respiratory medicine / Asthma, and allergies in children and adults

Academic & Professional Experience

  • 2016/03 - Today Graduate School of Medicine, Division of Respiratory Medicine

Education

  • 2013/04 - 2016/03  Hokkaido University Center for Environmental and Health Sicences
  • 2008/04 - 2013/03  Hokkaido University, Graduate School of Medicine, Institute For Genetic Medicine  Cancer Stem Cell Biology
  • 1997/02 - 2005/09  Tehran University, School of Medicine

Research Activities

Published Papers

  • Association between perfluoroalkyl substance exposure and thyroid hormone/thyroid antibody levels in maternal and cord blood: The Hokkaido Study.
    Itoh S, Araki A, Miyashita C, Yamazaki K, Goudarzi H, Minatoya M, Ait Bamai Y, Kobayashi S, Okada E, Kashino I, Yuasa M, Baba T, Kishi R
    Environ Int. 133(Pt A):105139. 2019/12 [Refereed][Not invited]
  • Multiple exposures to organophosphate flame retardants alter urinary oxidative stress biomarkers among children: The Hokkaido Study.
    Ait Bamai Y, Bastiaensen M, Araki A, Goudarzi H, Konno S, Ito S, Miyashita C, Yao Y, Covaci A, Kishi R
    Environ Int. 131:105003. 2019/10 [Refereed][Not invited]
  • Impact of Abdominal Visceral Adiposity on Adult Asthma Symptoms.
    Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M
    J Allergy Clin Immunol Pract. 7(4):1222-1229.e5. 2019/04 [Refereed][Not invited]
  • Houman Goudarzi, Satoshi Konno, Hirokazu Kimura, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yu Ait Bamai, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Yoichi M. Ito, Masaharu Nishimura, Reiko Kishi
    Science of the Total Environment 639 1601 - 1609 1879-1026 2018/10/15 [Refereed][Not invited]
     
    Background: Childhood allergies are dynamic and associated with environmental factors. The influence of prenatal maternal smoking and obesity on childhood allergies and their comorbidities remains unclear, especially in prospective cohorts with serial longitudinal observations. Objective: We examined time trends in the prevalence and comorbidity of childhood allergies, including wheeze, eczema, and rhinoconjunctivitis, using a large-scale, population-based birth cohort in Japan, and assessed the effects of prenatal maternal smoking and BMI on the risk of childhood allergies. Methods: Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires about symptoms of allergies and their risk factors at age 1, 2, 4, and 7 years. Complete data from all pre- and postnatal questionnaires at age 1, 2, 4, and 7 were available for 3296 mother–child pairs. Results: We observed significant overlap of childhood allergies at 1, 2, 4, and 7 years. Maternal serum cotinine during pregnancy was associated with increased risk of wheezing in the children at age 1, 2, and 4 but disappeared at age 7. In contrast, maternal cotinine levels were inversely associated with the prevalence of eczema in children at age 7. We additionally observed that maternal pre-pregnancy BMI, not children's BMI, had a positive association with wheeze and an inverse association with eczema in 7-year-old children, respectively. We did not find any association of examined maternal factors and rhinoconjunctivitis. Conclusions: We demonstrated contrasting association of prenatal maternal smoking and high BMI with postnatal wheeze and eczema. For precise assessment of allergy-associated risk factors, we need to contrast risk factors for different allergic diseases since focusing solely on one allergic disease may result in misleading information on the role of different risk factors.
  • Chihiro Miyashita, Atsuko Araki, Takahiko Mitsui, Sachiko Itoh, Houman Goudarzi, Seiko Sasaki, Jumboku Kajiwara, Tsuguhide Hori, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi
    Environment International 117 175 - 185 1873-6750 2018/08/01 [Refereed][Not invited]
     
    Background: Prenatal exposure to dioxin-like compounds (DLCs) irreversibly affects fetal reproductive and steroid hormone synthesis. Objective: This study aimed to assess the relationships between maternal DLCs and cord blood reproductive and steroid hormones. Methods: Participants in this study were pregnant women who enrolled in the Sapporo Cohort of the Hokkaido Study between 2002 and 2005. We quantified 29 DLCs during the 2nd and 3rd trimesters in maternal blood. Additionally, we measured the concentrations of progesterone, estradiol (E2), testosterone (T), androstenedione, dehydroepiandrosterone (DHEA), cortisol, cortisone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, inhibin B, and insulin-like factor-3 (INSL3) in cord blood samples. Results: Data from 183 mother-child pairs were analyzed. We observed sex-dependent associations of DLCs on T/E2 ratios, DHEA, cortisol, cortisone, adrenal androgen/glucocorticoid (AA/GC: sum of DHEA and androstenedione)/(sum of cortisol and cortisone) ratios and SHBG. An increase in maternal DLCs related to decreased T/E2 ratios and SHBG and inhibin B levels, and increased AA/GC ratios and FSH and DHEA levels in male cord blood samples. However, an increase in maternal mono-ortho polychlorinated biphenyls related to increased cortisol, cortisone, and SHBG levels, and decreased DHEA levels and AA/GC ratios in female cord blood samples. Conclusions: Prenatal exposure to DLCs alters steroidogenesis and suppresses the secretion of inhibin B in male cord blood. Relationships between maternal DLCs and cord blood hormones differ between boys and girls. Further studies are required to clarify whether the effects of in utero exposure to DLCs on adrenal hormones extend into infancy and puberty.
  • Mitsui T, Araki A, Goudarzi H, Miyashita C, Ito S, Sasaki S, Kitta T, Moriya K, Cho K, Morioka K, Kishi R, Shinohara N, Takeda M, Nonomura K
    American journal of human biology : the official journal of the Human Biology Council 30 (4) e23127  1042-0533 2018/07 [Refereed][Not invited]
  • Tetsuaki Shoji, Hidenori Mizugaki, Yasuyuki Ikezawa, Megumi Furuta, Yuta Takashima, Hajime Kikuchi, Houman Goudarzi, Hajime Asahina, Junko Kikuchi, Eiki Kikuchi, Jun Sakakibara-Konishi, Naofumi Shinagawa, Ichizo Tsujino, Masaharu Nishimura
    Internal medicine (Tokyo, Japan) 57 (12) 1769 - 1772 0918-2918 2018/06/15 [Refereed][Not invited]
     
    This report describes the case of a 66-year-old man with non-small cell lung cancer and venous thromboembolism (VTE). Unfractionated heparin (UFH) was initially used to control VTE before chemotherapy. However, switching UFH to warfarin or edoxaban, a novel oral anticoagulant (NOAC), failed. Chemotherapy was then administered to control the tumor which was thought to have been the main cause of VTE, which had been treated by UFH. After tumor shrinkage was achieved by chemotherapy, we were able to successfully switch from UFH to edoxaban. Controlling the tumor size and activity enabled the use of edoxaban as maintenance therapy for VTE.
  • Meng-Shan Tsai, Chihiro Miyashita, Atsuko Araki, Sachiko Itoh, Yu Ait Bamai, Houman Goudarzi, Emiko Okada, Ikuko Kashino, Hideyuki Matsuura, Reiko Kishi
    International journal of environmental research and public health 15 (5) 1661-7827 2018/05/14 [Refereed][Not invited]
     
    Perfluoroalkyl substances (PFAS) are persistent bio-accumulative chemicals that impact the health of pregnant women and their children. PFAS derive from environmental and consumer products, which depend on human lifestyle, socioeconomic characteristics, and time variation. Here, we aimed to explore the temporal trends of PFAS in pregnant women and the characteristics related to maternal PFAS concentration. Our study is part of the Hokkaido Study on Environment and Children's Health, the Hokkaido large-scale cohort that recruited pregnant women between 2003 and 2011. Blood samples were acquired from pregnant women during the third trimester to measure PFAS and cotinine concentrations. Maternal basic information was collected with a baseline structured questionnaire. Eleven PFAS were measured from 2123 samples with ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry. Eight PFAS were above 80% detection rate and were included in the final analysis. We used multivariable linear regression to analyze the association of pregnant women characteristics with the levels of eight PFAS. The temporal trend of PFAS was observed in two periods (August 2003 to January 2006 and February 2006 to July 2012). The concentration of perfluorooctane sulfonate (PFOS) significantly decreased from August 2003 to January 2006 and from February 2006 to July 2012. The concentrations of perfluorododecanoic acid (PFDoDA), perfluoroundecanoic acid (PFUnDA), and perfluorotridecanoic acid (PFTrDA) increased significantly between August 2003 and January 2006, whereas they decreased significantly between February 2006 and July 2012. Women with pre-pregnancy body mass index (BMI) >25 kg/m² had lower PFUnDA, PFDoDA, and PFTrDA levels than did those with normal BMI (18.5⁻24.9 kg/m²). Pregnant women, who were active smokers (cotinine > 11.49 ng/mL), had higher PFOS than the non-smokers (cotinine < 0.22 ng/mL). Lower levels of PFHxS, PFOS, PFOA, PFNA, and PFDA were observed in women, who had given birth to more than one child. There were also significant positive associations between PFAS levels and annual income or maternal education. PFAS levels varied in women with higher pre-pregnancy BMI, active smoking status, higher education level and annual income. The causes of the individual PFAS differences should be explored in an independent study.
  • Munehiro Matsumoto, Satoshi Konno, Hirokazu Kimura, Nozomu Takei, Hiroki Kimura, Kaoruko Shimizu, Houman Goudarzi, Masaru Suzuki, Satoshi Hashino, Masaharu Nishimura
    International Archives of Allergy and Immunology 176 (2) 143 - 149 1423-0097 2018/05/01 [Refereed][Not invited]
     
    Background: The coexistence of asthma and allergic rhinitis (AR) and its distinct association with obesity have been reported. However, few studies have differentiated the two types of AR, i.e., perennial (PAR) and seasonal AR (SAR), with regard to their associations with asthma and obesity. The aim of this study was to evaluate the coexistence of current wheeze and two types of AR and the impact of body mass index (BMI) on these two conditions in Japanese young adults. Methods: First-year students from Hokkaido University were enrolled into this study from 2011 to 2016. A questionnaire survey including the prevalence of current wheeze, PAR, and SAR every year for 11,917 nonsmoking young adults was conducted. The difference in the impact of current wheeze and BMI on these two types of AR was separately evaluated. Results: Although both PAR and SAR were significantly associated with current wheeze, the impact of these two AR types on current wheeze was different (OR for PAR = 2.46 vs. OR for SAR = 1.29). When we classified all of the subjects into 4 groups with or/and without the two types of AR, the prevalence of current wheeze was significantly higher in subjects with PAR than in those without PAR (p < 0.001). However, the prevalence of current wheeze did not differ between subjects with or without SAR. Multinomial regression analyses showed that the association of wheeze with PAR and/or SAR was stronger compared to that of wheeze with SAR without PAR. The prevalence of PAR was not associated with BMI. Contrarily, a low BMI was significantly associated with a high SAR prevalence (p < 0.05). Conclusion: Comparisons between PAR and SAR showed that the conditions are differentially associated with current wheeze and BMI.
  • Liew Z, Goudarzi H, Oulhote Y
    Current environmental health reports 5 (1) 1 - 19 2018/03 [Refereed][Invited]
  • Reiko Kishi, Atsuko Araki, Machiko Minatoya, Sachiko Itoh, Houman Goudarzi, Chihiro Miyashita
    SCIENCE OF THE TOTAL ENVIRONMENT 615 1143 - 1154 0048-9697 2018/02 [Refereed][Not invited]
     
    Asia contains half of the world's children, and the countries of Asia are the most rapidly industrializing nations on the globe. Environmental threats to the health of children in Asia are myriad. Several birth cohorts were started in Asia in early 2000, and currently more than 30 cohorts in 13 countries have been established for study. Cohorts can contain from approximately 100-200 to 20,000-30,000 participants. Furthermore, national cohorts targeting over 100,000 participants have been launched in Japan and Korea. The aim of this manuscript is to discuss the importance of Asian cohorts, and the advantages and disadvantages of different-sized cohorts. As for case, one small-sized (n = 514) cohort indicate that even relatively low level exposure to dioxin in utero could alter birth size, neurodevelopment, and immune and hormonal functions. Several Asian cohorts focus prenatal exposure to perfluoroalkyo substances and reported associations with birth size, thyroid hormone levels, allergies and neurodevelopment. Inconsistent findings may possibly be explained by the differences in exposure levels and target chemicals, and by possible statistical errors. In a smaller cohort, novel hypotheses or preliminary examinations are more easily verifiable. In larger cohorts, the etiology of rare diseases, such as birth defects, can be analyzed; however, they require a large cost and significant human resources. Therefore, conducting studies in only one large cohort may not always be the best strategy. International collaborations, such as the Birth Cohort Consortium of Asia, would cover the inherent limitation of sample size in addition to heterogeneity of exposure, ethnicity, and socioeconomic conditions. (C) 2017 Elsevier B.V. All rights reserved.
  • Atsuko Araki, Chihiro Miyashita, Takahiko Mitsui, Houman Goudarzi, Futoshi Mizutani, Youichi Chisaki, Sachiko Itoh, Seiko Sasaki, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi
    ENVIRONMENT INTERNATIONAL 110 1 - 13 0160-4120 2018/01 [Refereed][Not invited]
     
    Certain organochlorine pesticides (OCPs) are designated as persistent organic pollutants and are regulated in many countries. The effects of OCPs on pediatric endocrinology are a concern; however, only limited data exist from human studies on maternal OCP exposure and its effects on infants' hormone levels. This study was conducted as part of the Hokkaido Study Sapporo Cohort, a prospective birth cohort study in Japan. Participants included 514 women who enrolled at 23-35 weeks of gestation between 2002 and 2005; maternal blood samples were collected in late pregnancy, and 29 OCPs were measured. Reproductive and steroid hormone levels in cord blood were also determined. Characteristics of mothers and their infants were obtained from self-administered questionnaires and medical records. Ultimately, 232 samples with both OCP and hormone data were analyzed. Fifteen of 29 investigated OCPs were detected in over 80% of the samples, with p, p'-dichlorodiphenyldi-chloroethylene showing the highest concentration (median value: 619 pg/g-wet). The association between OCPs and sex hormone levels varied by sex. Linear regression models after sex stratification showed that chlordanes, cis-hexachlorobenzene, heptachlor epoxide, Mirex, and toxaphenes in maternal blood were inversely associated with testosterone, cortisol, cortisone, sex hormone-binding globin, prolactin, and androstenedione-dehydroepiandrosterone (DHEA) and testosterone-androstenediones ratios among boys. Furthermore, these OCPs were positively correlated with DHEA, follicle stimulating hormone (FSH), and adrenal androgen-glucocorticoid and FSH-inhibin B ratios among boys. In categorical quartile models, testosterone and DHEA were inversely and positively associated with OCPs, respectively. Estradiol-testosterone and adrenal androgen-glucocorticoid ratios tended to increase with increasing OCP concentrations in the higher quartile, while the testosterone-androstenedione ratio tended to decrease. Sex hormone-binding globulin and prolactin showed an inverse association with OCPs. Among girls, the linear regression model showed that only p, p'-dichlorodiphenyltrichloroethane was inversely associated with the level of DHEA and the adrenal androgen-glucocorticoid ratio, but was positively associated with cortisone levels. However, no associations were observed using the quartile categorical model. These results suggest that prenatal exposure to OCPs disrupt reproductive hormones of fetuses in utero among boys, even at relatively low levels.
  • Hirokazu Kimura, Satoshi Konno, Hironi Makita, Natsuko Taniguchi, Hiroki Kimura, Houman Goudarzi, Kaoruko Shimizu, Masaru Suzuki, Noriharu Shijubo, Katsunori Shigehara, Junya Ono, Kenji Izuhara, Yoichi Minagawa Ito, Masaharu Nishimura
    Allergology International 67 (3) 357 - 363 1440-1592 2018 [Refereed][Not invited]
     
    Background: Many studies have attempted to clarify the factors associated with serum periostin levels in asthmatic patients. However, these results were based on studies of subjects mainly characterized by high eosinophil counts, which may present as an obstacle for clarification in the identification of other factors associated with serum periostin levels. The aim of this study was to determine the factors associated with serum periostin levels in healthy subjects. We also assessed some factors in asthmatic subjects to confirm their extrapolation for management of asthma. Methods: Serum periostin levels were measured in 230 healthy subjects. Clinical factors of interest included body mass index (BMI) and allergic rhinitis (AR). Additionally, we confirmed whether these factors were associated with serum periostin in 206 asthmatic subjects. We further evaluated several obesity-related parameters, such as abdominal fat distribution and adipocytokine levels. Results: Smoking status, blood eosinophil count, total immunoglobulin E, and the presence of AR were associated with serum periostin in healthy subjects. There was a negative association between BMI and serum periostin in both healthy and asthmatic subjects, while there was a tendency of a positive association with AR in asthmatic subjects. There were no differential associations observed for subcutaneous and abdominal fat in relation to serum periostin in asthmatic subjects. Serum periostin was significantly associated with serum levels of adiponectin, but not with leptin. Conclusions: Our results provided clarity as to the factors associated with serum periostin levels, which could be helpful in the interpretation of serum periostin levels in clinical practice.
  • Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Titilola Serifat Braimoh, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Reiko Kishi
    REPRODUCTIVE TOXICOLOGY 74 94 - 103 0890-6238 2017/12 [Refereed][Not invited]
     
    Objectives: We aimed to assess the individual dose-response effects of eight maternal polymorphisms encoding polycyclic aromatic hydrocarbon-metabolizing and DNA-repair genes on prenatal cotinine levels according to infant birth size. Methods: In total, 3263 Japanese pregnant women were assigned to five groups based on plasma cotinine levels during the 8th month of pregnancy, as measured using ELISA (cut-offs: 0.21, 0.55, 11.48, and 101.67 ng/mL). Analyses were performed using multiple linear regression. Results: Birth weight reduction showed a dose-dependent relationship with prenatal cotinine levels (P for trend < 0.001). When considering the specific aromatic hydrocarbon receptor (AHR) (G >A, Arg554Lys; db SNP ID: rs2066853) and X-ray cross-complementing gene 1 (XRCC1) (C> T, Arg194Trp, rs1799782) genotypes, a larger birth weight reduction was noted among infants born to mothers with the highest cotinine level. Conclusion: Infants born to women with specific AHR and XRCC1 genotypes may have higher genetic risks for birth weight reduction. (C) 2017 Elsevier Inc. All rights reserved.
  • Titilola Serifat Braimoh, Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Houman Goudarzi, Thamar Ayo Yila, Atsuko Araki, Chihiro Miyashita, Hisanori Minakami, Tsuyoshi Baba, Kazuo Sengoku, Reiko Kishi
    SCIENCE OF THE TOTAL ENVIRONMENT 605 995 - 1002 0048-9697 2017/12 [Refereed][Not invited]
     
    Although the effects of prenatal passive smoking on birth weight have been reported, the effects of metabolic gene polymorphisms on passive smoking have not been studied. Therefore, we investigated the effects of maternal passive smoking and metabolic gene polymorphisms on child growth up to 3 years of age using cotinine as a biomarker. We included 1356 Japanese participants in a prospective cohort between 2003 and 2007 (cotinine levels at the third trimester <= 0.21 ng/mL and 0.22 to 11.48 ng/mL for non-passive and passive smokers, respectively), and measured child outcomes such as weight, length, head circumference, and Kaup index. Additionally, we analyzed cytochrome P450 1A1 (CYP1A1), epoxide hydrolase 1 (EPHX1), and two N-acetyltransferase 2 (NAT2) genotypes using real-time polymerase chain reaction methods. Associations were investigated using multiple regression models. Kaup index gain from birth up to 3 years of age was significantly smaller in children born to passive smokers than in those born to non-passive smokers (-0.34 kg/m(2); 95% confidence interval: -0.67, -0.01). Maternal CYP1A1 genotype was not associated with prenatal passive smoking and Kaup index gain, but was significantly associated with prenatal passive smoking and head circumference gain from birth up to 3 years of age (-0.75 cm; 95% confidence interval:-1.39, -0.12). Thus, this study suggests that prenatal passive smoking may have potent effects on postnatal growth frombirth up to 3 years of age. Moreover, children with maternal CYP1A1 genotype may be more susceptible to the effects of prenatal passive smoking. (C) 2017 Elsevier B.V. All rights reserved.
  • Sumitaka Kobayashi, Fumihiro Sata, Chihiro Miyashita, Ryu Miura, Kaoru Azumi, Sachiko Kobayashi, Houman Goudarzi, Atsuko Araki, Mayumi Ishizuka, Takashi Todaka, Jumboku Kajiwara, Tsuguhide Hori, Reiko Kishi
    TOXICOLOGY 390 135 - 145 0300-483X 2017/09 [Refereed][Not invited]
     
    Background: Associations between prenatal exposure to polychlorinated biphenyls (PCBs) and reduced birth size, and between DNA methylation of insulin-like growth factor-2 (IGF-2), HI 9 locus, and long interspersed nuclear element-1 (LINE-1) and reduced birth-size are well established. To date, however, studies on the associations between prenatal exposure to PCBs and alterations in methylation of IGF-2, H19, and LINE-1 are lacking. Thus, in this study, we examined these associations with infant-gender stratification. Methods: We performed a prospective birth cohort study using the Sapporo cohort from the previously described Hokkaido Birth Cohort Study on Environment and Children's Health conducted between 2002 and 2005 in Japan. In the final 169 study participants included in this study, we measured the concentrations of various non dioxin-like PCBs in maternal blood during pregnancy using high-resolution gas chromatography/high-resolution mass spectrometry. IGF-2, H19 and LINE-1 methylation levels in cord blood were measured using the bisulfite pyrosequencing methods Finally, we assessed the associations between prenatal exposure to various PCBs and the gene methylation levels using multiple regression models stratified by infant gender. Results: We observed a 0.017 (95% confidence interval [CI]: 0.003-0.031) increase in the log(10)-transformed H19 methylation levels (%) in cord blood for each ten-fold increase in the levels of decachlorinated biphenyls (decaCBs) in maternal blood among all infants. Similarly, a 0.005 (95% CI: 0.000-0.010) increase in the log(10)-transformed LINE-1 methylation levels (%) in cord blood was associated with each ten-fold increase in heptachlorinated biphenyls (heptaCBs) in maternal blood among all infants. In particular, we observed a dose-dependent association of the decaCB levels in maternal blood with the H19 methylation levels among female infants (P value for trend = 0.040); likewise a dose-dependent association of heptaCB levels was observed with LINE-I methylation levels among female infants (P value for trend = 0.015). Moreover, these associations were only observed among infants of primiparous women. Conclusion: Our results suggest that the dose-dependent association between prenatal exposure to specific non-dioxin-like PCBs and increases in the H19 and LINE-1 methylation levels in cord blood might be more predominant in females than in males.
  • Houman Goudarzi, Chihiro Miyashita, Emiko Okada, Ikuko Kashino, Chi-Jen Chen, Sachiko Ito, Atsuko Araki, Sumitaka Kobayashi, Hideyuki Matsuura, Reiko Kishi
    ENVIRONMENT INTERNATIONAL 104 132 - 138 0160-4120 2017/07 [Refereed][Not invited]
     
    Perfluoroalkyl acids (PFAAs) are synthetic chemicals with ability to repel oils and water, and have been widely used in many industrial and household applications such as adhesives and water-and stain-repellent surfaces to nonstick coatings. Animal studies have shown that PFAAs have immunotoxic effects. However, few epidemiological studies have investigated the effects of PFAAs on infectious diseases occurrence. We examined the relationship between prenatal exposure to PFAAs and prevalence of infectious diseases up to 4 years of life. A total of 1558 mother-child pairs, who were enrolled in the Hokkaido Study on Environment and Children's Health, were included in this data analysis. Eleven PFAAs were measured in maternal plasma taken at 28-32 weeks of gestation using ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. Participant characteristics were obtained from medical birth records and self-administered questionnaires during pregnancy and after delivery. Physicians' diagnosis of common infectious diseases including otitis media, pneumonia, respiratory syncytial virus infection, and varicella up to 4 years were extracted from the mother-reported questionnaires. The number of children who developed infectious diseases up to 4 years of age was as follows: otitis media, 649 (41.4%); pneumonia, 287 (18.4%); respiratory syncytial virus infection, 197 (12.6%); varicella 589 (37.8%). A total of 1046 (67.1%) children had at least one of the diseases defined as total infectious diseases. After adjusting for appropriate confounders, PFOS levels in the highest quartile were associated with increased odds ratios (ORs) of total infectious diseases (Q4 vs. Q1 OR: 1.61; 95% CI: 1.18, 2.21; p for trend = 0.008) in all children. In addition, perfluorohexane sulfonate (PFHxS) was associated with a higher risk of total infectious diseases only among girls (Q4 vs. Q1 OR: 1.55, 95% CI: 0.976, 2.45; p for trend = 0.045). We found no association between infectious diseases and other examined PFAAs. Our findings suggest that prenatal exposure to PFOS and PFHxS may associated with infectious diseases occurrence in early life. Therefore, prenatal exposure to PFAAs may be immunotoxic for the immune system in offspring. (C) 2017 Elsevier Ltd. All rights reserved.
  • Machiko Minatoya, Sachiko Itoh, Chihiro Miyashita, Atsuko Araki, Seiko Sasaki, Ryu Miura, Houman Goudarzi, Yusuke Iwasaki, Reiko Kishi
    ENVIRONMENTAL RESEARCH 156 175 - 182 0013-9351 2017/07 [Refereed][Not invited]
     
    Perfluoroalkyl substances (PFASs) are synthetic chemicals that persist in the environment and in humans. There is a possible association between prenatal PFASs exposure and both neonate adipokines and birth size, yet epidemiological studies are very limited. The objective of this study was to examine associations of prenatal exposure to PFASs with cord blood adipokines and birth size. We conducted birth cohort study, the Hokkaido Study. In this study, 168 mother-child pairs were included. Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in maternal blood were determined by liquid chromatography tandem mass spectrometry. Cord blood adiponectin and leptin levels were measured by ELISA and RIA, respectively. Birth weight and ponderal index (PI) were obtained from birth record. The median maternal PFOS and PFOA were 5.1 and 1.4 ng/ mL, respectively. The median total adiponectin and leptin levels were 19.4 mu g/mL and 6.2 ng/mL, respectively. Adjusted linear regression analyses found that PFOS level was positively associated with total adiponectin levels (beta=0.12, 95% CI:0.01, 0.22), contrary was negatively associated with PI (beta=-2.25, 95% CI:-4.01,- 0.50). PFOA level was negatively associated with birth weight (beta=-197, 95% CI:- 391,- 3). Leptin levels were not associated with PFASs levels. PFOS and adiponectin levels showed marginal dose-response relationship and both PFOS and PFOA and birth size showed significant dose-response relationships. Results from this study suggested that prenatal PFASs exposure may alter cord blood adiponectin levels and may decrease birth size.
  • Sachiko Kobayashi, Kaoru Azumi, Houman Goudarzi, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Itoh, Seiko Sasaki, Mayumi Ishizuka, Hiroyuki Nakazawa, Tamiko Ikeno, Reiko Kishi
    JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY 27 (3) 251 - 259 1559-0631 2017/05 [Refereed][Not invited]
     
    Prenatal exposure to perfluoroalkyl acids (PFAAs) influences fetal growth and long-term health. However, whether PFAAs affect offspring DNA methylation patterns to influence health outcomes is yet to be evaluated. Here, we assessed effect of prenatal PFAA exposure on cord blood insulin-like growth factor 2 (IGF2), H19, and long interspersed element 1 (LINE1) methylation and its associations with birth size. Mother-child pairs (N = 177) from the Hokkaido Study on Environment and Children's Health were included in the study. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) levels in maternal serum were measured by liquid chromatography-tandem mass spectrometry. IGF2, H19, and LINE1 methylation in cord blood DNA was determined by pyrosequencing. After full adjustment in multiple linear regression models, IGF2 methylation showed a significant negative association with log-unit increase in PFOA (partial regression coefficient = -0.73; 95% confidence interval: -1.44 to -0.02). Mediation analysis suggested that reduced IGF2 methylation explained similar to 21% of the observed association between PFOA exposure and reduced ponderal index of the infant at birth. These results indicated that the effects of prenatal PFOA exposure could be mediated through DNA methylation. Further study will be required to determine the potential for long-term adverse health effects of reduced IGF2 methylation induced by PFOA exposure.
  • Atsuko Araki, Takahiko Mitsui, Houman Goudarzi, Tamie Nakajima, Chihiro Miyashita, Sachiko Itoh, Seiko Sasaki, Kazutoshi Cho, Kimihiko Moriya, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi
    SCIENCE OF THE TOTAL ENVIRONMENT 581 297 - 304 0048-9697 2017/03 [Refereed][Not invited]
     
    Di(2-ethylhexyl) phthalate (DEHP) is known for its endocrine disrupting properties. We previously demonstrated that prenatal DEHP exposure is associated with decreased progesterone levels and testosterone/estradiol ratio in the cord blood. However, evidence of the effects of prenatal DEHP exposure on adrenal androgen and glucocorticoids in infants is scarce. Thus, the objectives of this study were to investigate the association between prenatal DEHP exposure and adrenal androgen and glucocorticoids, and to discuss its effects on steroid hormone profiles in infants. This is part of a birth cohort study: The Hokkaido Study on Environment and Children's Health, Sapporo Cohort. Among the 514 participants, 202 mother-infant pairs with available data on maternal mono (2ethylhexyl) phthalate (MEHP), adrenal androgen (dehydroepiandrostenedione [DHEA] and androstenedione) and glucocorticoid (cortisol and cortisone) cord blood levels were included in this study. After adjusting for potential confounders, a linear regression analysis showed that maternal MEHP levels were associated with reduced cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio, whereas increased DHEA levels and DHEA/androstenedione ratio. In a quartile model, when comparing the adjusted least square means in the 4th quartile of MEHP with those in the 1st quartile, cortisol and cortisone levels and glucocorticoid/adrenal androgen ratio decreased, whereas DHEA/androstenedione and cortisol/cortisone ratios increased. Significant p-value trends for cortisol and cortisone levels, cortisol/cortisone ratio, and glucocorticoid/adrenal androgen ratio were observed. In combination with the previous results of reduced progesterone levels and testosterone/estradiol ratio, prenatal exposure to DEHP altered the steroid hormone profiles of infants. Further studies investigating the long-term effects of DEHP exposure on growth, neurodevelopment, and gonad and reproductive function are required. (C) 2016 Elsevier B.V. All rights reserved.
  • Houman Goudarzi, Atsuko Araki, Sachiko Itoh, Seiko Sasaki, Chihiro Miyashita, Takahiko Mitsui, Hiroyuki Nakazawa, Katsuya Nonomura, Reiko Kishi
    ENVIRONMENTAL HEALTH PERSPECTIVES 125 (1) 111 - 118 0091-6765 2017/01 [Refereed][Not invited]
     
    BACKGROUND: Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans. OBJECTIVES: We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones. METHODS: We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother-infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way. RESULTS: We found a dose-response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were -23.98-ng/mL (95% CI: -0.47.12, -11.99; p for trend = 0.006) and -63.21-ng/mL (95% CI: -132.56, -26.72; p for trend < 0.001) lower, respectively, in infants with prenatal PFOS exposure in the fourth quartile compared with those in the first quartile. The highest quartile of prenatal PFOS exposure was positively associated with a 1.33-ng/mL higher DHEA level compared with the lowest quartile (95% CI: 0.17, 1.82; p for trend = 0.017), whereas PFOA showed a negative association with DHEA levels (quartile 4 vs. quartile 1: -1.23 ng/mL, 95% CI: -1.72, -0.25; p for trend = 0.004). We observed no significant association between PFCs and androstenedione levels. CONCLUSIONS: Our results indicate that prenatal exposure to PFCs is significantly associated with glucocorticoid and DHEA levels in cord blood.
  • Sumitaka Kobayashi, Fumihiro Sata, Chihiro Miyashita, Seiko Sasaki, Susumu Ban, Atsuko Araki, Houman Goudarzi, Jumboku Kajiwara, Takashi Todaka, Reiko Kishi
    REPRODUCTIVE TOXICOLOGY 67 111 - 116 0890-6238 2017/01 [Refereed][Not invited]
     
    Objectives: We investigated the effects of maternal polymorphisms in 3 genes encoding dioxin metabolizing enzymes in relation to prenatal dioxin levels on infant birth size in Japan. Methods: We examined the relationship between dioxin exposure and birth size in relation to the polymorphisms in the genes encoding aromatic hydrocarbon receptor (AHR [G > A, Arg554Lys]), cytochrome P450 (CYP) 1A1 (T6235C), and glutathione S-transferase mu I (GSTM1; Non-null/null) in 421 participants using multiple linear regression models. Results: In mothers carrying the GSTM1 null genotype, a ten-fold increase in total dioxin toxic equivalency was correlated with a decrease in birth weight of -345g (95% confidence interval: -584, -105). Conclusions: We observed adverse effects of maternal GSTM1 null genotype on birth weight in the presence of dioxins exposure during pregnancy. (C) 2016 Elsevier Inc. All rights reserved.
  • Reiko Kishi, Atsuko Araki, Machiko Minatoya, Tomoyuki Hanaoka, Chihiro Miyashita, Sachiko Itoh, Sumitaka Kobayashi, Yu Ait Bamai, Keiko Yamazaki, Ryu Miura, Naomi Tamura, Kumiko Ito, Houman Goudarzi
    ENVIRONMENTAL HEALTH AND PREVENTIVE MEDICINE 22 (1) 46  1342-078X 2017 [Refereed][Not invited]
     
    The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary study goals are (1) to examine the effects of low-level environmental chemical exposures on birth outcomes, including birth defects and growth retardation; (2) to follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders and perform a longitudinal observation of child development; (3) to identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) to identify the additive effects of various chemicals, including tobacco smoking. The purpose of this report is to update the progress of the Hokkaido Study, to summarize the recent results, and to suggest future directions. In particular, this report provides the basic characteristics of the cohort populations, discusses the population remaining in the cohorts and those who were lost to follow-up at birth, and introduces the newly added follow-up studies and case-cohort study design. In the Sapporo cohort of 514 enrolled pregnant women, various specimens, including maternal and cord blood, maternal hair, and breast milk, were collected for the assessment of exposures to dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluoroalkyl substances, phthalates, bisphenol A, and methylmercury. As follow-ups, face-to-face neurobehavioral developmental tests were conducted at several different ages. In the Hokkaido cohort of 20,926 enrolled pregnant women, the prevalence of complicated pregnancies and birth outcomes, such as miscarriage, stillbirth, low birth weight, preterm birth, and small for gestational age were examined. The levels of exposure to environmental chemicals were relatively low in these study populations compared to those reported previously. We also studied environmental chemical exposure in association with health outcomes, including birth size, neonatal hormone levels, neurobehavioral development, asthma, allergies, and infectious diseases. In addition, genetic and epigenetic analyses were conducted. The results of this study demonstrate the effects of environmental chemical exposures on genetically susceptible populations and on DNA methylation. Further study and continuous follow-up are necessary to elucidate the combined effects of chemical exposure on health outcomes.
  • Sumitaka Kobayashi, Fumihiro Sata, Seiko Sasaki, Titilola Serifat Braimoh, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi, Sachiko Kobayashi, Reiko Kishi
    REPRODUCTIVE TOXICOLOGY 65 295 - 306 0890-6238 2016/10 [Refereed][Not invited]
     
    Objectives: We investigated the individual and combined effects of maternal polymorphisms encoding the aromatic hydrocarbon receptor (AHR; rs2066853), cytochrome P450 (CYP) 1A1 (rs1048963), and the X-ray-complementing gene 1 (XRCC1; rs1799782) and prenatal smoking in relation to infant birth size. Methods: Totally, 3263 participants (1998 non-smokers and 1265 smokers) were included in the study between 2003 and 2007. Two groups of mothers were distinguished by plasma cotinine levels by ELISA measured during the third trimester (cut-off= 11.48 ng/mL). We conducted data analysis using multiple linear regression models. Results: Infants whose mothers smoked and had AHR-GG, CYP1A1-AG/GG, and XRCC1-CT/TT genotypes weighed, -145 g less than those born of mothers who did not smoke and had the AHR-GA/AA, CYP1A1-AA, and XRCC1-CC genotypes (95% CI: 241, 50). Conclusions: We demonstrated that infants whose mothers smoked during pregnancy with the combination of AHR, CYP1A1, and XRCC1 polymorphisms had lower birth size. (C) 2016 Elsevier Inc. All rights reserved.
  • Sachiko Itoh, Atsuko Araki, Takahiko Mitsui, Chihiro Miyashita, Houman Goudarzi, Seiko Sasaki, Kazutoshi Cho, Hiroyuki Nakazawa, Yusuke Iwasaki, Nobuo Shinohara, Katsuya Nonomura, Reiko Kishi
    ENVIRONMENT INTERNATIONAL 94 51 - 59 0160-4120 2016/09 [Refereed][Not invited]
     
    Background: Exposure to perfluoroalkyl substances (PFASs) may disrupt reproductive function in animals and humans. Although PFASs can cross the human placental barrier, few studies evaluated the effects of prenatal PFAS exposure on the fetus' reproductive hormones. Objective: To explore the associations of prenatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) with cord blood reproductive hormones. Methods: In the prospective birth cohort (Sapporo cohort of the Hokkaido study), we included 189 mother-infant pairs recruited in 2002-2005 with both prenatal maternal and cord blood samples. PFOS and PFOA levels in maternal blood after the second trimester were measured via liquid chromatography-tandem mass spectrometry. We also measured cord blood levels of the fetuses' reproductive hormones, including estradiol (E2), total testosterone (T), progesterone (P4), inhibin B, insulin-like factor 3, steroid hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone, and prolactin (PRL). Results: The median PFOS and PFOA levels in maternal serum were 5.2 ng/mL and 1.4 ng/mL, respectively. In the fully adjusted linear regression analyses of the male infants, maternal PFOS levels were significantly associated with E2 and positively, and T/E2, P4, and inhibin B inversely; PFOA levels were positively associated with inhibin B levels. Among the female infants, there were significant inverse associations between PFOS levels and P4 and PRL levels, although there were no significant associations between PFOA levels and the female infants' reproductive hormone levels. Conclusions: These results suggest that the fetal synthesis and secretion of reproductive hormones may be affected by in utero exposure to measurable levels of PFOS and PFOA. (C) 2016 Elsevier Ltd. All rights reserved.
  • Houman Goudarzi, Chihiro Miyashita, Emiko Okada, Ikuko Kashino, Sumitaka Kobayashi, Chi-Jen Chen, Sachiko Ito, Atsuko Araki, Hideyuki Matsuura, Yoichi M. Ito, Reiko Kishi
    ENVIRONMENT INTERNATIONAL 94 124 - 132 0160-4120 2016/09 [Refereed][Not invited]
     
    Perfluoroalkyl acids (PFAAs) are ubiquitous chemicals extremely resistant and widespread throughout the environment, frequently being detected in human blood samples. Animal studies have revealed that exposure to PFAAs results in immunotoxicity. However, the association between PFAAs, especially long-chain PFAAs, and allergies in humans is not well established. We examined whether prenatal exposure to PFAAs is associated with allergic diseases among 4-year-old children in a large-scale prospective birth cohort in Hokkaido, Japan. In total, 1558 mother-child pairs were included in this study and prenatal levels of eleven PFAAs were measured in maternal plasma samples obtained between 28 and 32 weeks of pregnancy by using ultra-performance liquid chromatography-tandem mass spectrometry. Participant demographic and characteristic information were obtained from self-administered pre- and postnatal questionnaires and medical birth records. Infant allergies were assessed using the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three questionnaire, which was administered 4 years post-delivery. Symptoms included eczema, wheezing and rhinoconjunctivitis with a prevalence of 19.0%, 18.7%, and 5.4%, respectively. Associations of PFAA quartiles with allergic outcomes were examined using logistic models. Adjusted odds ratios (ORs) in the 4th quartile vs. 1st quartile (Q4 vs. Q1) for total allergic diseases (including at least one allergic outcome) significantly decreased for perfluorododecanoic acid (PFDoDa) (Q4 vs. Q1 OR: 0.621; 95% confidence interval (CI): 0.454, 0.847) andperfluorotridecanoic acid (PFTrDA) (Q4 vs. Q1 OR: 0.712; 95% CI: 0.524, 0.966) in all children. We obtained similar results when examining the association between PFAAs and eczema. The adjusted OR (Q4 vs. Q1) for wheezing in relation to higher maternal PFHxS levels was 0.728 (95% CI: 0.497, 1.06) in all children. In conclusion, prenatal exposure to long-chain PFAAs, such as PFDoDa and PFTrDA may have an immunosuppressive effect on allergic diseases in 4-year-old children. (C) 2016 Published by Elsevier Ltd.
  • Takahiko Mitsui, Atsuko Araki, Houman Goudarzi, Chihiro Miyashita, Sachiko Ito, Seiko Sasaki, Takeya Kitta, Kimihiko Moriya, Kazutoshi Cho, Keita Morioka, Reiko Kishi, Nobuo Shinohara, Masayuki Takeda, Katsuya Nonomura
    STEROIDS 113 46 - 51 0039-128X 2016/09 [Refereed][Not invited]
     
    Objectives: We investigated the relationship between the levels of adrenal steroid hormones in cord blood and the second to fourth digit ratio (2D/4D), which is regarded as an indirect method to investigate the putative effects of prenatal exposure to androgens, in school-aged children. Materials and methods: Of the 514 mother-child pairs who participated in the prospective cohort study of birth in Sapporo between 2002 and 2005, the following adrenal steroid hormone levels in 294 stored cord blood samples (135 males and 159 females) were measured; cortisol, cortisone, androstenedione and dehydroepiandrosterone (DHEA). A total of 190 out of 350 children who were currently school-aged and contactable for this survey sent back photocopies of their palms for 2D/4D measurements. Results: 2D/4D in all right hands, left hands, and mean values was significantly lower in males than in females (p < 0.01). DHEA levels were significantly higher in females. A multivariate regression model showed that 2D/4D negatively correlated with DHEA in males only (p < 0.01). No correlations were observed in the other adrenal steroid hormones tested in males or in any adrenal steroid hormones in females. Conclusion: DHEA is mainly secreted in large amounts by the adrenal gland and is transformed into active sex-steroid hormones in peripheral tissues. The present study demonstrated that sex differences in digits were influenced by adrenal androgens during the prenatal period, possibly through intracrinological processes for androgen receptors located in fetal cartilaginous tissues. (C) 2016 Elsevier Inc. All rights reserved.
  • Thamar A. Yila, Atsuko Araki, Seiko Sasaki, Chihiro Miyashita, Kumiko Itoh, Tamiko Ikeno, Eiji Yoshioka, Sumitaka Kobayashi, Houman Goudarzi, Toshiaki Baba, Titilola Braimoh, Hisanori Minakami, Toshiaki Endo, Kazuo Sengoku, Reiko Kishi
    BRITISH JOURNAL OF NUTRITION 115 (12) 2227 - 2235 0007-1145 2016/06 [Refereed][Not invited]
     
    The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children's Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1.48; 95% CI 1.32, 1.66), lower educational level (AOR 1.27; 95% CI 1.17, 1.39) and lower annual income (AOR 1.11; 95% CI 1.01, 1.22). Plasma cotinine concentrations of 1.19-65.21 nmol/l increased the risk of low folate status (AOR 1.20; 95% CI 1.10, 1.31) and concentrations > 65.21 nmol/l further increased the risk (AOR 1.91; 95% CI 1.70, 2.14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0.19; 95% CI 0.17, 0.22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women.
  • Houman Goudarzi, Sonomi Nakajima, Tamiko Ikeno, Seiko Sasaki, Sachiko Kobayashi, Chihiro Miyashita, Sachiko Ito, Atsuko Araki, Hiroyuki Nakazawa, Reiko Kishi
    SCIENCE OF THE TOTAL ENVIRONMENT 541 1002 - 1010 0048-9697 2016/01 [Refereed][Not invited]
     
    Perfluorinated chemicals (PFCs) are ubiquitous and persistent pollutants widely detected in blood samples of animals and humans across the globe. Although animal studies have shown the potential neurotoxicity of PFCs, there are few epidemiological studies regarding neurological effects of PFCs in humans, and those studies have had inconclusive results. In this study, we conducted a hospital-based prospective birth cohort study between 2002 and 2005 (n = 514) to examine the associations between prenatal perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) exposures and the neurodevelopment of infants at 6 (n = 173) and 18 (n = 133) months of age. Using the second edition of the Bayley Scales of Infant Development (BSID II), the Mental and Psychomotor Developmental Indices (MDI and PDI, respectively) were assessed. PFOS and PFOA were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. After controlling for confounders, prenatal PFOA concentrations were associated with the MDI of female (but not male) infants at 6 months of age (beta = -0.296; 95% confidence interval (CI): -11.96, -0.682). Furthermore, females born to mothers with prenatal concentrations of PFOA in the fourth quartile had MDI scores -5.05 (95% CI: -10.66 to 0.55) lower than females born to mothers with concentrations of PFOA in the first quartile (p for trend = 0.045). However, PFOA concentrations were not significantly associated with neurodevelopmental indices at 18 months of age. In addition, we did not observe any significant association between PFOS concentrations and neurodevelopmental outcomes in early infancy. In conclusion, our results suggest that prenatal PFOA exposure may affect female mental scales of neurodevelopment at 6 months of age. Further studies with larger sample sizes and longer observation periods are required to clarify sex difference of the neurodevelopmental effects. (C) 2015 Elsevier B.V. All rights reserved.
  • Reiko Kishi, Tamie Nakajima, Houman Goudarzi, Sachiko Kobayashi, Seiko Sasaki, Emiko Okada, Chihiro Miyashita, Sachiko Itoh, Atsuko Araki, Tamiko Ikeno, Yusuke Iwasaki, Hiroyuki Nakazawa
    ENVIRONMENTAL HEALTH PERSPECTIVES 123 (10) 1038 - 1045 0091-6765 2015/10 [Refereed][Not invited]
     
    BACKGROUND: Fatty acids (FAs) are essential for fetal growth. Exposure to perfluorinated chemicals (PFCs) may disrupt FA homeostasis, but there are no epidemiological data regarding associations of PFCs and FA concentrations. OBJECTIVES: We estimated associations between perfluorooctane sulfonate (PFOS)/perfluoro-octanoate (PFOA) concentrations and maternal levels of FAs and triglyceride (TG) and birth size of the offspring. METHODS: We analyzed 306 mother-child pairs in this birth cohort between 2002 and 2005 in Japan. The prenatal PFOS and PFOA levels were measured in maternal serum samples by liquid chromatography-tandem mass spectrometry. Maternal blood levels of nine FAs and TG were measured by gas chromatography-mass spectrometry and TG E-Test Wako kits, respectively. Information on infants' birth size was obtained from participant medical records. RESULTS: The median PFOS and PFOA levels were 5.6 and 1.4 ng/mL, respectively. In the fully adjusted model, including maternal age, parity, annual household income, blood sampling period, alcohol consumption, and smoking during pregnancy, PFOS but not PFOA had a negative association with the levels of palmitic, palmitoleic, oleic, linoleic, alpha-linolenic, and arachidonic acids (p < 0.005) and TG (p-value = 0.016). Female infants weighed 186.6 g less with mothers whose PFOS levels were in the fourth quartile compared with the first quartile (95% CI: -363.4, -9.8). We observed no significant association between maternal levels of PFOS and birth weight of male infants. CONCLUSIONS: Our data suggest an inverse association between PFOS exposure and polyunsaturated FA levels in pregnant women. We also found a negative association between maternal PFOS levels and female birth weight.
  • Houman Goudarzi, Hisashi Iizasa, Masako Furuhashi, Seitaro Nakazawa, Rie Nakane, Shanshan Liang, Yasuhiro Hida, Kazuyoshi Yanagihara, Takanori Kubo, Koji Nakagawa, Masanobu Kobayashi, Tatsuro Irimura, Jun-ichi Hamada
    CANCER LETTERS 339 (1) 82 - 92 0304-3835 2013/10 [Refereed][Not invited]
     
    In this study, we examined the effects of hypoxia on the malignancy of human malignant pleural mesothelioma (MPM) cell lines, and found (I) hypoxia enhanced motility and invasiveness of human malignant pleural mesothelioma (MPM) cells; (2) this phenomenon resulted from increased expression of sialylated MUC1 through the activation of HIF-1 pathway; (3) two HIF-binding sites located in the promoter region of MUC1 were important for MUC1 transactivation under hypoxia. These findings are useful for better understanding molecular mechanisms of aggressive behavior of MPM cells and for targeting them in the clinical therapies for MPM patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
  • Shanshan Liang, Masako Furuhashi, Rie Nakane, Seitaro Nakazawa, Houman Goudarzi, Jun-ichi Hamada, Hisashi Iizasa
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 437 (2) 205 - 211 0006-291X 2013/07 [Refereed][Not invited]
     
    Sex determining region Y-box 2 (SOX2) is well known as one of the "sternness" factors and is often expressed in cancers including breast cancer. In this study, we developed a reporter system using fluorescent protein driven by the promoter for SOX2 gene to detect and isolate living SOX2-positive cells. Using this system, we determined that SOX2 promoter activities were well correlated with SOX2 mRNA expression levels in 5 breast cancer cell lines, and that the cell population with positive SOX2 promoter activity (pSp-T+) isolated from one of the 5 cell lines, MCF-7 cells, showed a high SOX2 protein expression and high sphere-forming activity compared with very low promoter activity (pSp-Tlow/-). The pSp-T(+)pbpulation expressed higher mRNA levels of several stemness-related genes such as CD44, ABCB1, NANOG and TWIST] than the pSp-Tlow/- population whereas the two populations expressed CD24 at similar levels. These results suggest that the cell population with SOX2 promoter activity contains cancer stem cell (CSC)-like cells which show different expression profiles from those of CSC-marker genes previously recognized in human breast cancers. (C) 2013 Elsevier Inc. All rights reserved.
  • Houman Goudarzi, Yasuhiro Hida, Hiroko Takano, Hiroki Teramae, Hisashi Iizasa, Jun-ichi Hamada
    BIOMEDICAL RESEARCH-TOKYO 34 (1) 13 - 21 0388-6107 2013/02 [Refereed][Not invited]
     
    Human malignant pleural mesothelioma (MPM) is highly aggressive, and its prognosis is very poor. For an early diagnosis of MPM and developing new therapeutic strategies against the malignancy, it is necessary to better understand biological characteristics of MPM. In this study, we established two cell lines from pleural effusions derived from patients with MPM. Both cell lines expressed tumor markers of mesothelioma such as mesothelin, podoplanin, WT1, calretinin and keratin 5/6 whereas they did not express either CEA or TTF-1 which are often used as markers of lung adenocarcinoma. The cell lines harboured wild-type TP53, produced hyaluronic acid, and were not infected with SV40. When these two cell lines were cultured under hypoxia (1% O-2), they showed particular responses to the hypoxic condition, distinct from those to normoxic condition (21% O-2). Namely, the ability to form a colony originating from a single cell (plating efficiency and cloning efficiency) was stimulated under hypoxia in both cell lines. On the other hand, when the assays of cell growth were started at a relatively high cell density, the growth of both cell lines, regardless of anchorage-dependent or -independent, decreased under hypoxia. The differences of their growth between under hypoxia and under normoxia, and those depending on the cell density, may provide useful hints for developing a new strategy for diagnosis or therapy of MPM.

Conference Activities & Talks

  • Mixture Chemical Exposure in Utero and Boys Reproductive Hormone Levels at Birth: the Hokkaido study.  [Not invited]
    Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Takahiko Mitsui, Houman Goudarzi, Kazutoshi Cho, Kimihiko Moriya, Tamie Nakajima, Yusuke Iwasaki, Tsuguhide Hori, Junboku Kajiwara, Nobuo Shinohara, Reiko Kishi
    2019/10
  • Childhood allergies and obesity relationship: identification of non-invasive biomarkers.  [Not invited]
    Houman Goudarzi, Satoshi Konno, Atsuko Araki, Sachiko Ito, Yu Ait Bamai, Chihiro Miyashita, Reiko Kishi
    European Respiratory Society International Congress, Madrid, Spain.  2019/09
  • EFFECT OF PRENATAL EXPOSURE TO PERFLUOROALKYL SUBSTANCES (PFAS) ON CHILDHOOD ALLERGIES: THE HOKKAIDO STUDY.  [Not invited]
    Ait Bamai Yu, Goudarzi Houman, Okada Emiko, Araki Atsuko, Miyashita Chihiro, Matsuura Hideyuki, Kishi Reiko
    39th International Symposium on Halogenated Persistent Organic Pollutants, Kyoto, Japan.  2019/08
  • English proficiency improvement in Japanese medical students using Omnibus style English exposure.  [Not invited]
    Houman Goudarzi, Masahiro Onozawa, Junji Otaki
    The 51st Annual Meeting of the Japan Society for Medical Education (JSME)  2019/07
  • Contrasting associations of maternal smoking and pre-pregnancy BMI with wheeze and eczema in children.  [Invited]
    Goudarzi Houman, 荒木敦子, 伊藤 佐智子, アイツバマイゆふ, 宮下ちひろ, 木村孔一, 今野 哲, 岸 玲子
    2019/06
  • Differential impact of obesity indices on systemic and sputum inflammatory biomarkers among asthma patients.  [Not invited]
    Houman Goudarzi, Satoshi Konno, Hironi Makita, Hirokazu Kimura, Munehiro Matsumoto, Nozomu Takei, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Masaharu Nishimura
    The 59th Annual Meeting of the Japanese Respiratory Society, Tokyo, Japan.  2019/04
  • Distinct impact of abdominal visceral adiposity on asthma symptoms.  [Not invited]
    Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Nishimura M
    European Respiratory Society International Congress, Paris, France  2018/09
  • Effect of prenatal exposure to perfluoroalkyl substances on childhood infectious diseases up to 7 years of age: The Hokkaido Study.  [Not invited]
    Ait Bamai Y, Miyashita C, Okada E, Kashino I, Araki A, Goudarzi H, Matsuura H, Kishi R
    The Joint Annual Meeting of the International Society of Exposure Science and the International Society for Environmental Epidemiology (ISES-ISEE), Ottawa, Canada  2018/08
  • Contrasting associations of maternal smoking and BMI with wheeze and eczema in children.  [Not invited]
    Goudarzi H, Konno S, Kimura H, Araki A, Miyashita C, Itoh S, Ait Bamai Y, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M, Kishi R
    Japanese Society of Allergology (JSA) 67th Annual Meeting, Chiba, Japan.  2018/06
  • Prenatal exposure to perfluorinated alkyl substances and childhood ADHD risk at 6 years old: the Hokkaido Study on Environment and Children’s Health.  [Not invited]
    Yamazaki K, Itoh S, Araki A, Miyashita C, Minatoya M, Tamura N, Goudarzi H, Okada E, Kashino I, Kishi R
    Meeting of the International Society of Exposure Science and the International Society for Environmental Epidemiology (ISES-ISEE), Asia Chapter, Taipei, Taiwan  2018/06
  • Distinct impact of abdominal visceral adiposity on asthma symptoms.  [Not invited]
    Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Nishimura M
    The 58th Annual Meeting of the Japanese Respiratory Society, Osaka, Japan.  2018/04
  • Potential roles of club cell 16-kDa secretory protein (CC16) and CC chemokine ligand 18 (CCL18) in obese severe asthmatic patients.  [Not invited]
    Goudarzi H, Konno S, Makita H, Kimura H, Kimura H, Shimizu K, Suzuki M, Nishimura M
    Japanese Society of Allergology (JSA) 66th Annual Meeting, Tokyo, Japan.  2017/06
  • Potential roles of club cell 16-kDa secretory protein (CC16) and CC chemokine ligand 18 (CCL18) in obese severe asthmatic patients.  [Not invited]
    Goudarzi H, Konno S, Makita H, Kimura H, Kimura H, Shimizu K, Suzuki M, Nishimura M
    American Thoracic Society (ATS) International Conference, Washington, USA  2017/05
  • Maternal exposure to endocrine disrupting chemicals (perfluoro-alkyls, phthalates and PCB/dioxins) and children’s reproductive hormone levels at birth; the Hokkaido Study on Environments and Children’s Health.  [Invited]
    Kishi R, Araki A, Miyashita C, Itoh S, Goudarzi H
    25th EPICOH - Epidemiology in Occupation Health Conference, Spain  2016/09
  • Effects of prenatal exposure to perfluoroalkyl acids on risk of allergic and infectious diseases in early life.  [Not invited]
    Goudarzi H, Miyashita C, Okada E, Kashino I, Kobayashi S, Chen CJ, Ito S, Araki A, Matsuura H, Ito YM, Kishi R
    28th conference for International Society for Environmental Epidemiology (ISEE), Rome, Italy  2016/09
  • Combined effects of AHR, CYP1A1 and XRCC1 genetic polymorphisms and prenatal maternal smoking on infant birth size: The Hokkaido Study on Environmental and Children’s Health.  [Not invited]
    Kobayashi Su, Sata F, Sasaki S, Braimoh TS, Araki A, Miyashita C, Goudarzi H, Kobayashi Sa, Kishi R
    ISEE-ISES AC, Sapporo, Japan  2016/06
  • Endocrine Disruption Effect of perfluoroalkyl substances exposure in utero: Hokkaido Study on Environment and Children’s Health.  [Not invited]
    Itoh S, Araki A, Miyashita C, Goudarzi H, Kato S, Iwasaki Y, Nakazawa H, Shinohara N, Kishi R
    ISEE-ISES AC 2016, Sapporo, Japan.  2016/06
  • Effects of prenatal exposure to perfluoroalkyl acids on risk of allergic and infectious diseases in early life.  [Not invited]
    Goudarzi H, Miyashita C, Okada E, Kashino I, Kobayashi S, Chen CJ, Ito S, Araki A, Matsuura H, Ito YM, Kishi R
    ISEE-ISES AC 2016 June 26-29, Sapporo, Japan.  2016/06
  • Effects of environmental exposure and genetic polymorphisms on children’s birth size.  [Invited]
    Goudarzi H, Kishi R, Araki A
    The 18th Hokkaido University (HU) and Seoul National University (SNU) Joint Symposium. Seoul, South Korea.  2015/11
  • Exposure to perfluoroalkyl chemicals and neurodevelopment at 6 months of age  [Invited]
    Goudarzi H, Ikeno T, Kobayashi S, Araki A, Miyashita C, Sasaki S, Nakajima S, Nakazawa H, Kishi R
    The 18th Hokkaido University (HU) and Seoul National University (SNU) Symposium, Seoul, South Korea  2015/11
  • The Association of Prenatal Exposure to Perfluorinated Chemicals with Maternal Fatty Acids during Pregnancy and the Birth Weight of their Offspring: The Hokkaido Study.  [Not invited]
    Goudarzi H, Kishi R, Nakajima T, Kobayashi S, Miyashita C, Itoh S, Araki A
    27th conference for International Society for Environmental Epidemiology, Sao Paulo, Brazil.  2015/09
  • Perinatal PFAAs exposure cause various health outcomes on offspring: the Hokkaido study.  [Invited]
    Kishi R, Araki A, Miyashita C, Itoh S, Goudarzi H, Kobayashi S
    8th Copenhagen workshops on Endocrine Disruptors, Copenhagen, Denmark.  2015/04
  • Perinatal PFAAs Exposure Cause Various Health Outcomes on Offspring Including Effects on Reproductive and Thyroid Hormones: The Hokkaido Study.  [Not invited]
    Kishi R, Araki A, Itoh S, Miyashita C, Goudarzi H, Kobayashi S, Sasaki S, Kashino I, Nakazawa H, Nakajima T, Mitsui T, Nonomura K
    Pptox IV, Boston, USA.  2014/10
  • Exposure to perfluoroalkyl chemicals and neurodevelopment at 6 months of age.  [Not invited]
    Goudarzi H, Ikeno T, Kobayashi S, Araki A, Miyashita C, Sasaki S, Nakajima S, Nakazawa H, Kishi R
    26th conference for International Society for Environmental Epidemiology, Seattle, USA.  2014/08
  • The effects of perfluoroalkyl acids (PFAAs) exposure in utero on IGF2/H19 DNA methylation in cord blood.  [Not invited]
    Houman Goudarzi
    26th conference for International Society for Environmental Epidemiology, Seattle, USA.  2014/08

Research Grants & Projects

  • 環境研究総合推進費 (研究分担者)、 環境省、 日本
    Date (from‐to) : 2017/04 -2019/05 
    Author : Atsuko Araki, Reiko Kishi, Satoshi Konno, Houman Goudarzi
  • Grant-in-Aid for Young Scientists B (若手B) as Principal Investigator, JSPS, Japan
    Date (from‐to) : 2017/04 -2019/03 
    Author : Houman Goudarzi
  • 6) 環境研究総合推進費 (研究分担者)、 環境省、 日本
    Date (from‐to) : 2014/04 -2017/03 
    Author : Reiko Kishi, Atsuko Araki, Chihiro Miyashita, Houman Goudarzi
  • Grant-in-Aid for JSPS fellow(日本学術振興会 外国人特別研究員)Japan Society for the Promotion of Science
    Date (from‐to) : 2014/10 -2016/03 
    Author : Houman Goudarzi
  • Challenging Exploratory Research (挑戦的萌芽研究, 研究分担者), JSPS, Japan
    Date (from‐to) : 2014/04 -2016/03 
    Author : Atsuko Araki, Houman Goudarzi
  • Grant-in-Aid for Young Scientists B (若手B) as Principal Investigator, JSPS, Japan (2014)
    Date (from‐to) : 2014/04 -2014/10 
    Author : Houman Goudarzi
  • Grant-in-Aid for Research Activity Start-up (研究活動スタート支援) as Principal Investigator, JSPS, Japan (2013)
    Date (from‐to) : 2013/04 -2014/03 
    Author : Houman Goudarzi

Educational Activities

Teaching Experience

  • 医学総論
    開講年度 : 2019
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • 医学英語演習
    開講年度 : 2019
    課程区分 : 学士課程
    開講学部 : 医学部


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