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Effects of exposure to environmental chemicals on adolescent reproductive function, depression, and NCDs in the Hokkaido Study: Clarification of molecular mechanism

Research Project

Project/Area Number 22H00489
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 58:Society medicine, nursing, and related fields
Research InstitutionHokkaido University

Principal Investigator

岸 玲子  北海道大学, 環境健康科学研究教育センター, センター特別招へい教授 (80112449)

Co-Investigator(Kenkyū-buntansha) 齊藤 卓弥  北海道大学, 大学病院, 特任教授 (20246961)
池田 敦子  北海道大学, 保健科学研究院, 教授 (00619885)
山崎 圭子  北海道大学, 環境健康科学研究教育センター, 特任講師 (60732120)
田村 菜穂美  北海道大学, 環境健康科学研究教育センター, 特任講師 (80836164)
山口 健史  北海道大学, 環境健康科学研究教育センター, 特任准教授 (80894972)
宮下 ちひろ  北海道大学, 環境健康科学研究教育センター, 客員研究員 (70632389)
伊藤 佐智子  北海道大学, 環境健康科学研究教育センター, 客員研究員 (90580936)
アイツバマイ ゆふ  北海道大学, 環境健康科学研究教育センター, 特任准教授 (90752907)
小林 澄貴  北海道大学, 環境健康科学研究教育センター, 客員研究員 (10733371)
Project Period (FY) 2022-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2024)
Budget Amount *help
¥43,680,000 (Direct Cost: ¥33,600,000、Indirect Cost: ¥10,080,000)
Fiscal Year 2024: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2023: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2022: ¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Keywords環境化学物質 / 出生コーホート / 青年期 / NCDs / 精神疾患
Outline of Research at the Start

本研究は20年間追跡している出生コーホート「環境と子どもの健康に関する研究・北海道スタディ(北海道スタディ)」において、現在の社会的課題の克服、および将来の疾病予防の達成を目指して、青年期以降の追跡および健康・疾病アウトカム評価を行う。本研究では生涯の健康向上と疾病リスク低減を念頭に、環境要因と青年期以降の体格や睡眠、甲状腺や性ホルモン、脂質糖代謝、および月経不順や月経困難症などの将来の生殖能力に関与する多様なアウトカムを評価する。将来の非感染性疾患や神経発達障害、不妊を含むリプロダクティブヘルス、若年層で深刻な社会問題であるうつ等の精神疾患の早期兆候と環境要因との関連を明らかにする。

Outline of Annual Research Achievements

本研究では20年間に渡り追跡している出生コーホート研究を用い、胎児期および生後の環境化学物質による曝露を含む環境要因による次世代影響の解明を目的として、将来の非感染性疾患(NCDs; Non-Communicable Diseases、循環器疾患や糖尿病など)や神経発達障害、不妊を含むリプロダクティブヘルス(性と生殖に関する健康)、若年層で深刻な社会問題であるうつ等の精神疾患の早期兆候と環境要因との関連を明らかにする。
2023年度は、コーホートの参加者について12歳で第二次性徴に関する調査票1,030件、12歳で小学校の学校健診記録から転記する身長体重調査票1,012件、15歳で中学校の身長体重調査票1,183件、17歳のアレルギーと体格の質問票1,322件を発送した。回収数は、12歳第二次性徴686件(回収率66.6%)、12歳身長体重は672件(回収率66.4%)、14歳359件(回収率31.5%)、15歳611件(回収率51.6%)17歳757件(回収率57.3%)であった。郵送法で12歳の対象者から271件の尿試料を回収した。18歳の調査の本人の同意に関して1360件の発送を行い、667件(回収率51.6%)の返送があり、同意354件、不同意313件を得た。
14-17歳の参加者39名を対象に、対面調査を実施した。参加者はアレルギーおよび身の周りの日用品の使用頻度等に関する調査票に回答し、採血、採尿を実施した。また、睡眠や活動量等を測定するため、Fitbitを着用して対面調査から1週間のデータ収集を実施した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

大規模出生コーホートの調査継続、質問票の発送および回収に関しては概ね計画通りに進んでいる。青年期の対象者のリクルートを継続すると共に、青年期のアウトカムである主観的健康感、社会的問題行動の評価を行い、次年度の環境化学物質の曝露に関する生体試料の評価につなげる。

Strategy for Future Research Activity

引き続き出生コーホートの調査継続、青年期の参加者のリクルート、質問票の発送および回収、フォローアップの維持を継続する。2024年度は収集したアウトカムのデータをもとに、環境化学物質の曝露に関する生体試料の評価を行う計画である。最終的には、胎児期および生後の環境化学物質による曝露を含む環境要因による次世代影響の解明を目的として、将来の非感染性疾患や神経発達障害、不妊を含むリプロダクティブヘルス(性と生殖に関する健康)、若年層で深刻な社会問題であるうつ等の精神疾患の早期兆候と環境要因との関連を明らかにする。
これまでの対面調査で得られた尿や血液検体の生体試料については、化学物質ばく露測定および健康アウトカムと関連するバイオマーカーの分析を検討する。具体的には、昨年度までに測定を終えた、7歳時点の尿中の有機リン系農薬、ネオニコチノイド系農薬代謝物濃度と13歳の脳波および8歳の注意欠如・多動症との関連について解析する。また、9-12歳児約430名分の尿中フタル酸エステル類およびPFR代謝物、ビスフェノール類、PFAS等の分析が済んでいるので、NCDsの原因となる肥満等の健康アウトカムや性ホルモン濃度との関連を検討する。子どもの思春期の肥満と出産時の臍帯血で測定したエピジェネティクス等の分子機構の関連についても解明することを目指す。

Report

(3 results)
  • 2023 Annual Research Report
  • 2022 Comments on the Screening Results   Annual Research Report
  • Research Products

    (28 results)

All 2023 2022 Other

All Journal Article (5 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (22 results) (of which Int'l Joint Research: 13 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Exposure to organophosphate flame retardants and plasticizers is positively associated with wheeze and FeNO and eosinophil levels among school-aged children: The Hokkaido study2023

    • Author(s)
      Zeng Yi、Goudarzi Houman、Ait Bamai Yu、Ketema Rahel Mesfin、Roggeman Maarten、den Ouden Fatima、Gys Celine、Miyashita Chihiro、Ito Sachiko、Konno Satoshi、Covaci Adrian、Kishi Reiko、Ikeda-Araki Atsuko
    • Journal Title

      Environment International

      Volume: 181 Pages: 108278-108278

    • DOI

      10.1016/j.envint.2023.108278

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exposure Trends to the Non-phthalate Plasticizers DEHTP, DINCH, and DEHA in Children from 2012 to 2017: The Hokkaido Study2023

    • Author(s)
      Ketema Rahel Mesfin、Kasper-Sonnenberg Monika、Ait Bamai Yu、Miyashita Chihiro、Koch Holger M.、Palmke Claudia、Kishi Reiko、Ikeda Atsuko
    • Journal Title

      Environmental Science and Technology

      Volume: 57 Issue: 32 Pages: 11926-11936

    • DOI

      10.1021/acs.est.3c03172

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential determinants of T helper 2 markers and their distribution in school-aged children2023

    • Author(s)
      Goudarzi Houman、Ikeda-Araki Atsuko、Bamai Yu Ait、Ito Sachiko、Inao Tasuku、Yokota Isao、Miyashita Chihiro、Kishi Reiko、Konno Satoshi
    • Journal Title

      Allergology International

      Volume: 72 Issue: 1 Pages: 100-106

    • DOI

      10.1016/j.alit.2022.07.009

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of exposure to prenatal per?uoroalkyl substances and estrogen receptor 1 polymorphisms with the second to fourth digit ratio in school-aged children: The Hokkaido study2022

    • Author(s)
      Nishimura Yoko、Moriya Kimihiko、Kobayashi Sumitaka、Ikeda- Araki Atsuko、Sata Fumihiro、Mitsui Takahiko、Itoh Sachiko、Miyashita Chihiro、Cho Kazutoshi、Kon Masafumi、Nakamura Michiko、Kitta Takeya、Murai Sachiyo、Kishi Reiko、Shinohara Nobuo
    • Journal Title

      Reproductive Toxicology

      Volume: 109 Pages: 10-18

    • DOI

      10.1016/j.reprotox.2022.02.002

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nonylphenol exposure in 7-year-old Japanese children between 2012 and 2017? Estimation of daily intakes based on novel urinary metabolites2022

    • Author(s)
      Ringbeck Benedikt、Bury Daniel、Ikeda-Araki Atsuko、Ait Bamai Yu、Ketema Rahel Mesfin、Miyashita Chihiro、Br?ning Thomas、Kishi Reiko、Koch Holger M.
    • Journal Title

      Environment International

      Volume: 161 Pages: 107145-107145

    • DOI

      10.1016/j.envint.2022.107145

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Exposure to Organophosphate Flame Retardants and their Associations with Allergic Symptoms and Type 2 Inflammation Biomarkers: The Hokkaido Study.2023

    • Author(s)
      Zeng Y., Ikeda A., Goudarzi H., Ait Bamai Y., Ketema RM., Roggeman M., Fatima Den Ouden., Miyashita C., Ito S., Konno S., Covaci A., Kishi R.
    • Organizer
      HU UoM joint research workshop on Environmental Experience Design for Active Ageing. Commonwealth of Australia.
    • Related Report
      2023 Annual Research Report
  • [Presentation] The Association between Urinary Phthalates and Use of Plastic Utensils in School Children: Hokkaido Study on Environment and Children’s Health.2023

    • Author(s)
      Zeng Y., Ait Bamai Y., Ketema RM., Yamaguchi T., Miyashita C., Ito S., Kishi R., Ikeda A.
    • Organizer
      The 6th FHS International Conference.
    • Related Report
      2023 Annual Research Report
  • [Presentation] Childrens environmental health The Hokkaido Study on Environment and Children’s Health - overview of environmental chemical exposure in utero and children’s health up to school age.2023

    • Author(s)
      Ikeda A., Ait Bamai Y., Miyashita C., Kishi R.
    • Organizer
      International Conference on the Environmenta, Work and Health in the 21th Century: Strategies and Solutions to a Global Crisis.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Children’s Exposure to DEHTP, DINCH, and DEHA: Results the Hokkaido Cohort Study2023

    • Author(s)
      Ketema RM., Kasper-Sonnenberg M., Ait Bamai Y., Miyashita C., Koch HM., Palmke C., Kishi R., Ikeda-Araki A.
    • Organizer
      35th Annual Conference of International Society for Environmental Epidemiology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The relationship of endocrine-disrupting chemicals exposure with oxidative stress biomarkers among Japanese school children : The hokkaido Study2023

    • Author(s)
      Ketema RM., Ait Bamai Y., Ikeda A., Kishi R.
    • Organizer
      35th Annual Conference of International Society for Environmental Epidemiology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Hokkaido Cohort Study findngs on the assosiation of exposure to organaphosphate flame retardants, bisphenols, nonyl phenol, and phthalates with oxidative stress.2023

    • Author(s)
      Ketema RM., Ait Bamai Y., Ikeda A., Kishi R.
    • Organizer
      2023 International Symposium of Precision Environmental Medicine (ISPEM)/Birth Cohort Consortium of Asia (BiCCA) Workshop and Reunion.
    • Related Report
      2023 Annual Research Report
  • [Presentation] Organophosphate Flame Retardants Mixture associated with Increased Urinary Oxidative Stress Biomarkers among School Children: The Hokkaido Study.2023

    • Author(s)
      Ikeda A., Ait Bamai Y., Yamaguchi T., Gys C., Roggeman M., Fatima Den Ouden., Ikenaka Y., Zeng Y., Ketema RM., Marsela M., Miyashita C., Covaci A., Kishi R.
    • Organizer
      35th Annual Conference of International Society for Environmental Epidemiology.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Hokkaido Study on Environment and Children’s Study: overview of environmental chemical exposures in utero and children’s health up to school age2023

    • Author(s)
      Ikeda A., Ait Bamai Y., Miyashita C., Kishi R.
    • Organizer
      35th Annual Conference of International Society for Environmental Epidemiology.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] WHO Collaborating Centre for Environmental Health and Prevention of Chemical Hazards - Social implementation from birth cohort studies.2023

    • Author(s)
      Ikeda A., Ketema RM., Kishi R.
    • Organizer
      2023 International Symposium of Precision Environmental Medicine (ISPEM)/Birth Cohort Consortium of Asia (BiCCA) Workshop and Reunion.
    • Related Report
      2023 Annual Research Report
  • [Presentation] Organophosphate Flame Retardants Mixture Associated with Increased Urinary Oxidative Stress Biomarkers among School Children: The Hokkaido Study.2023

    • Author(s)
      Zeng Y., Goudarzi H., Ait Bamai Y., Ketema RM., Roggeman M., Fatima Den Ouden., Miyashita C., Ito S., Konno S., Covaci A., Kishi R., Ikeda A.
    • Organizer
      35th Annual Conference of International Society for Environmental Epidemiology.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Environmental exposures and neurodevelopmental outcomes: findings from cohort studies. “Prenatal exposure to toxic environmental chemicals associated with neurodevelopmental outcomes: Findings from the Hokkaido Study”.2023

    • Author(s)
      Ikeda A., Kishi R.
    • Organizer
      The 18th Congress of Asian Society for Pediatric Research (ASPR).
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Protect your children from early exposure to environmental chemicals - from the Hokkaido birth cohort studies and implications for policies/guidelines.2023

    • Author(s)
      Ikeda A.
    • Organizer
      World Health City Forum.
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 北海道スタディ、思春期小児調査からみえる、将来的なNon-communicable Diseasesリスク.2023

    • Author(s)
      山口健史、曾怡、池田敦子、Rahel Mesfin Ketema、アイツバマイゆふ、宮下ちひろ、今雅史、中村明枝、岸玲子.
    • Organizer
      第75回北海道公衆衛生学会.
    • Related Report
      2023 Annual Research Report
  • [Presentation] 「環境化学物質と健康障害の予防」に関する世界保健機関研究協力センター(WHO Collaboragting Centre)の紹介.2023

    • Author(s)
      池田敦子、Rahel Mesfin Ketema、山﨑圭子、田村菜穂美、山本理恵子、岸玲子.
    • Organizer
      第75回北海道公衆衛生学会.
    • Related Report
      2023 Annual Research Report
  • [Presentation] 環境化学物質曝露と次世代影響:出生コーホート研究「環境と子どもの健康に関する北海道スタディ」より.2023

    • Author(s)
      池田敦子、宮下ちひろ、アイツバマイゆふ、伊藤佐智子、岸玲子.
    • Organizer
      日本薬学会第143回年会.
    • Related Report
      2023 Annual Research Report
  • [Presentation] Impact of PFAS on childhood asthma and allergies and infectious diseases: the Hokkaido Study on Environment and Children’s Health.2022

    • Author(s)
      Ait Bamai Y., Miyashita C., Kishi R.
    • Organizer
      Impacts of early Life Exposure to Environmental Contaminants: Children’s Health in the Anthropocene.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Internal and external exposure levels of legacy and alternative plasticizers among Japanese children and the contributions of house dust to urinary metabolites: The Hokkaido Study.2022

    • Author(s)
      Ait Bamai Y., Inaba Y., Covaci A., Ketema RM., Ikeda-Araki A., Bekki K., Kim H., Kishi R.
    • Organizer
      International Society of Exposure Science.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Mixture exposure to plastic-related short half-life chemicals and associations with childhood asthma and allergies: The Hokkaido Study.2022

    • Author(s)
      Ait Bamai Y., Gys C., Bastiaensen M., Ikeda-Araki A., Ketema RM., Goudarzi H., Miyashita C., Konno S., Covaci A., Kishi R.
    • Organizer
      34th Annual Conference of the International Society for Environmental Epidemiology (ISEE).
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Associations between bisphenols and onset of puberty: the Hokkaido Study.2022

    • Author(s)
      Ikeda-Araki A., Ait Bamai Y., Gys C., M Roggeman, Ikenaka Y., Yamaguchi T., Masuda H., Miyashita C., Nakamura A., Kitta T., Manabe A., Shinohara N., Covaci A., Kishi R.
    • Organizer
      The 34th annual conference of the International Society for Environmental Epidemiology (ISEE2022).
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of environmental chemical exposure on childhood asthma and allergies, and infections.2022

    • Author(s)
      Ikeda-Araki A., Ait Bamai Y., Miyashita C., Kishi R.
    • Organizer
      2022 PBC Conference “Enviromental exposures in a Chaging Climate”.
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 胎児期フタル酸エステル類曝露による思春期発来への影響―北海道スタディ.2022

    • Author(s)
      山口健史、池田敦子、アイツバマイゆふ、宮下ちひろ、中村明枝、今雅史、藤谷倫子、原田浩二.
    • Organizer
      第9回日本DOHaD学会.
    • Related Report
      2022 Annual Research Report
  • [Presentation] 学童のプラスチック添加剤への曝露実態 :北海道スタディ.2022

    • Author(s)
      池田敦子、アイツバマイゆふ、Rahel Mesfin Ketema、Celine Gys、Michiel Bastiaensen、Adrian Covaci、岸玲子.
    • Organizer
      第92回日本衛生学会学術総会.
    • Related Report
      2022 Annual Research Report
  • [Remarks] 環境と子どもの健康に関する研究:北海道スタディ

    • URL

      https://www.cehs.hokudai.ac.jp/hokkaidostudy/

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report

URL: 

Published: 2022-04-19   Modified: 2024-12-25  

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