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Effects of prenatal exposure to endocrine disruption chemicals on gonadal function and sexual dimorphism

Research Project

Project/Area Number 17K11171
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionHokkaido University

Principal Investigator

Moriya Kimihiko  北海道大学, 医学研究院, 客員研究員 (20374233)

Co-Investigator(Kenkyū-buntansha) 中村 美智子  北海道大学, 大学病院, 助教 (60571718)
篠原 信雄  北海道大学, 医学研究院, 教授 (90250422)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords性分化 / 内分泌かく乱物質 / 胎児期曝露 / 遺伝子多型 / ESR1遺伝子 / 内分泌かく乱化学物質 / エストロゲン受容体 / 一塩基多型 / 第2指と第4指の比 / 環境化学物質 / 排泄の確立 / 性分化・環境化学物質 / 胎児期 / 性腺機能
Outline of Final Research Achievements

It has been reported that some endocrine disrupting chemicals has estrogenic effect. In the present study, effect of prenatal exposure of the endocrine disrupting chemicals on sexual differentiation and its modification by single nucleotide polymorphism of estrogen receptor gene (ESR1-SNP) were examined. Digit ratio of 2nd and 4th finger (2D:4D) was utilizes as a maker of sex differentiation in the present study because it has been reported to be affected by prenatal exposure of sex hormones. First, impact of ESR1-SNP on 2D:4D was evaluated. Then, effect of phthalate esters and Bisphenol A, which were demonstrated to have estrogenic effect in previous studies, and ESR1-SNP on 2D:4D was estimated.
As results, rs9340799, one of the ESR1-SNP, affected 2D:4D. Phthalate esters affected 2D:4D in boys with G allele of rs2077647, one of the ESR1-SNP.

Academic Significance and Societal Importance of the Research Achievements

本研究の検討から、エストロゲン様作用を有するとされるEDCsへの胎児期曝露が性分化へ与える影響は単に曝露量のみではなくESR1遺伝子SNPの影響を受けていることが示唆された。本研究の結果はEDCsの胎児期曝露の影響が出やすいSNPを有する群が存在する可能性を示している。現在、環境化学物質曝露と停留精巣や尿道下裂などの小児泌尿器科疾患との関連が注目されている。本研究は、胎児期EDCs曝露による性分化への影響を受ける可能性の高い母児の抽出に役立つのみならず、彼らに対する曝露低減や生活習慣指導など、今後の予防対策・環境政策に寄与する可能性があると考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (37 results)

All 2020 2019 2018 2017

All Journal Article (25 results) (of which Peer Reviewed: 22 results,  Open Access: 14 results) Presentation (12 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Pediatric congenital hydronephrosis (ureteropelvic junction obstruction): Medical management guide2020

    • Author(s)
      Kohno Miyuki、Ogawa Tetsushi、Kojima Yoshiyuki、Sakoda Akiko、Johnin Kazuyoshi、Sugita Yoshifumi、Nakane Akihiro、Noguchi Mitsuru、Moriya Kimihiko、Hattori Motoshi、Hayashi Yutaro、Kubota Masayuki
    • Journal Title

      International Journal of Urology

      Volume: なし Issue: 5 Pages: 369-376

    • DOI

      10.1111/iju.14207

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of exposure to prenatal phthalate esters and bisphenol A and polymorphisms in the ESR1 gene with the second to fourth digit ratio in school-aged children: Data from the Hokkaido study2020

    • Author(s)
      Nishimura Yoko、Moriya Kimihiko、Kobayashi Sumitaka、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

      Steroids

      Volume: 159 Pages: 108637-108637

    • DOI

      10.1016/j.steroids.2020.108637

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dopaminergic urethral closure mechanisms in a rat model of Parkinson's disease.2019

    • Author(s)
      Ouchi M, Kitta T, Kanno Y, Higuchi M, Togo M, Takahashi Y, Moriya K, Shinohara N.
    • Journal Title

      Neurourol Urodyn.

      Volume: - Issue: 5 Pages: 1203-1211

    • DOI

      10.1002/nau.23989

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic nephroureterectomy using the stoma site of cutaneous ureterostomy as a multi-channel port site in a 15-month-old child with megaureter: A case report2019

    • Author(s)
      Nakamura Michiko、Moriya Kimihiko、Kon Masafumi、Nishimura Yoko、Kitta Takeya、Shinohara Nobuo
    • Journal Title

      Urology Case Reports

      Volume: 27 Pages: 100990-100990

    • DOI

      10.1016/j.eucr.2019.100990

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with hypospadias.2019

    • Author(s)
      Moriya K, Nakamura M, Kon M, Nishimura Y, Kanno Y, Kitta T, Shinohara N.
    • Journal Title

      World J Urol.

      Volume: - Issue: 12 Pages: 2795-2799

    • DOI

      10.1007/s00345-019-02687-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【泌尿器科疾患に伴う尿細管間質障害】閉塞性腎症2019

    • Author(s)
      守屋 仁彦
    • Journal Title

      腎と透析

      Volume: 87 Pages: 340-344

    • Related Report
      2019 Annual Research Report
  • [Journal Article] シンポジウム3.成育的観点から見た小児泌尿器科診療 3.成育医療の観点から見た尿道下裂2019

    • Author(s)
      守屋 仁彦、中村 美智子、今 雅史、篠原信雄
    • Journal Title

      泌尿器外科

      Volume: 32 Pages: 586-587

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Ⅶ 膀胱拡大術 回腸利用膀胱拡大術2019

    • Author(s)
      守屋 仁彦
    • Journal Title

      Urologic Surgery Next

      Volume: 5 Pages: 144-153

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Effects of prenatal sex hormones on behavioral sexual dimorphism.2019

    • Author(s)
      Mitsui T, Araki A, Miyashita C, Ito S, Ikeno T, Sasaki S, Kitta T, Moriya K, Cho K, Morioka K, Kishi R, Shinohara N, Takeda M, Nonomura K.
    • Journal Title

      Pediatr Int.

      Volume: 61 Issue: 2 Pages: 140-146

    • DOI

      10.1111/ped.13756

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association between ESR1 polymorphisms and second to fourth digit ratio in school-aged children in the Hokkaido Study.2019

    • Author(s)
      Nishimura Y, Moriya K, Kobayashi S, Araki A, Sata F, Mitsui T, Itoh S, Miyashita C, Cho K, Kon M, Nakamura M, Kitta T, Murai S, Kishi R, Shinohara N.
    • Journal Title

      Steroids

      Volume: 141 Pages: 55-62

    • DOI

      10.1016/j.steroids.2018.11.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence and risk factors of testicular microlithiasis in patients with hypospadias: a retrospective study.2018

    • Author(s)
      Nakamura M, Moriya K, Nishimura Y, Nishida M, Kudo Y, Kanno Y, Kitta T, Kon M, Shinohara N.
    • Journal Title

      BMC Pediatr

      Volume: 18 Issue: 1 Pages: 179-179

    • DOI

      10.1186/s12887-018-1151-6

    • NAID

      120006491520

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex-related differences in the associations between maternal dioxin-like compounds and reproductive and steroid hormones in cord blood: The Hokkaido study.2018

    • Author(s)
      Miyashita C, Araki A, Mitsui T, Itoh S, Goudarzi H, Sasaki S, Kajiwara J, Hori T, Cho K, Moriya K, Shinohara N, Nonomura K, Kishi R.
    • Journal Title

      Environ Int

      Volume: 117 Pages: 175-185

    • DOI

      10.1016/j.envint.2018.04.046

    • NAID

      120006876269

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Medium-term follow-up after supervised pelvic floor muscle training for patients with anterior vaginal wall prolapse.2018

    • Author(s)
      Ouchi M, Kitta T, Kanno Y, Moriya K, Suzuki S, Shinohara N, Kato K
    • Journal Title

      Eur J Obstet Gynecol Reprod Biol

      Volume: 225 Pages: 95-100

    • DOI

      10.1016/j.ejogrb.2018.04.015

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term Outcome of Adenosine A2A Receptor Antagonist on Lower Urinary Tract Symptoms in Male Parkinson Disease Patients.2018

    • Author(s)
      Kitta T, Yabe I, Kanno Y, Higuchi M, Ouchi M, Togo M, Moriya K, Takahashi I, Matsushima M, Sasaki H, Shinohara N.
    • Journal Title

      Clin Neuropharmacol

      Volume: 41 Issue: 3 Pages: 98-102

    • DOI

      10.1097/wnf.0000000000000281

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between adrenal steroid hormones in cord blood and birth weight: The Sapporo Cohort, Hokkaido Study on Environment and Children's Health2018

    • Author(s)
      Mitsui Takahiko、Araki Atsuko、Goudarzi Houman、Miyashita Chihiro、Ito Sachiko、Sasaki Seiko、Kitta Takeya、Moriya Kimihiko、Cho Kazutoshi、Morioka Keita、Kishi Reiko、Shinohara Nobuo、Takeda Masayuki、Nonomura Katsuya
    • Journal Title

      American Journal of Human Biology

      Volume: - Issue: 4

    • DOI

      10.1002/ajhb.23127

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of a 5-HT2c receptor agonist on urethral closure mechanisms in female rats.2018

    • Author(s)
      Ouchi Mifuka, Kitta Takeya, Kanno Yukiko, Higuchi Madoka, Togo Mio, Moriya Kinmihiko, Sinohara Nobuo
    • Journal Title

      Neurourol Urodyn.

      Volume: - Issue: 8 Pages: 2382-2388

    • DOI

      10.1002/nau.23586

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: The Hokkaido study2018

    • Author(s)
      Araki Atsuko、Miyashita Chihiro、Mitsui Takahiko、Goudarzi Houman、Mizutani Futoshi、Chisaki Youichi、Itoh Sachiko、Sasaki Seiko、Cho Kazutoshi、Moriya Kimihiko、Shinohara Nobuo、Nonomura Katsuya、Kishi Reiko
    • Journal Title

      The Hokkaido study. Environ Int.

      Volume: 110 Pages: 1-13

    • DOI

      10.1016/j.envint.2017.10.006

    • NAID

      120006776798

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact of Preoperative Ultrasonographic Evaluation for Detection of a Viable Testis in Patients With a Unilateral Nonpalpable Testis2017

    • Author(s)
      Moriya Kimihiko、Nakamura Michiko、Nishimura Yoko、Nishida Mutsumi、Kudo Yusuke、Kanno Yukiko、Kitta Takeya、Kon Masafumi、Shinohara Nobuo
    • Journal Title

      J Ultrasound Med

      Volume: - Issue: 7 Pages: 1665-1670

    • DOI

      10.1002/jum.14509

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of posterior urethral diameter/external urethral sphincter diameter as a new tool to predict detrusor pressure in the voiding phase2017

    • Author(s)
      Kon Masafumi、Mitsui Takahiko、Kitta Takeya、Moriya Kimihiko、Shinohara Nobuo、Takeda Masayuki、Nonomura Katsuya
    • Journal Title

      Int Urol Nephrol.

      Volume: 50 Issue: 2 Pages: 211-215

    • DOI

      10.1007/s11255-017-1770-0

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence and Chronological Changes of Testicular Microlithiasis in Isolated Congenital Undescended Testes Operated On at Less Than 3 Years of Age2017

    • Author(s)
      Nishimura Yoko、Moriya Kimihiko、Nakamura Michiko、Nishida Mutsumi、Sato Megumi、Kudo Yusuke、Omotehara Satomi、Iwai Takahito、Wakabayashi Yamato、Kanno Yukiko、Kitta Takeya、Kon Masafumi、Shinohara Nobuo
    • Journal Title

      Urology

      Volume: 109 Pages: 159-164

    • DOI

      10.1016/j.urology.2017.07.035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children's Health.2017

    • Author(s)
      Minatoya M, Sasaki S, Araki A, Miyashita C, Itoh S, Yamamoto J, Matsumura T, Mitsui T, Moriya K, Cho K, Morioka K, Minakami H, Shinohara N, Kishi R.
    • Journal Title

      Epidemiology.

      Volume: - Pages: S3-S9

    • DOI

      10.1097/ede.0000000000000716

    • NAID

      120006536947

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prevalence of and risk factors for symptomatic urinary tract infection after endoscopic incision for the treatment of ureterocele in children2017

    • Author(s)
      Moriya Kimihiko、Nakamura Michiko、Nishimura Yoko、Kanno Yukiko、Kitta Takeya、Kon Masafumi、Shinohara Nobuo
    • Journal Title

      BJU Int

      Volume: 120 Issue: 3 Pages: 409-415

    • DOI

      10.1111/bju.13884

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic ureterocalicostomy for ureteropelvic junction obstruction in a 10-year-old female patient: a case report2017

    • Author(s)
      Nishimura Yoko、Moriya Kimihiko、Nakamura Michiko、Kitta Takeya、Kanno Yukiko、Chiba Hiroki、Kon Masafumi、Shinohara Nobuo
    • Journal Title

      BMC Res Notes.

      Volume: 10 Issue: 1 Pages: 247-247

    • DOI

      10.1186/s13104-017-2569-x

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spontaneous Shrinkage of Testicular Teratoma in a Prepubertal Child2017

    • Author(s)
      Moriya Kimihiko、Yamamoto Shota、Nakamura Michiko、Nishimura Yoko、Nishida Mutsumi、Iwai Takahito、Kanno Yukiko、Kitta Takeya、Shinohara Nobuo
    • Journal Title

      Urology

      Volume: 103 Pages: e13-e14

    • DOI

      10.1016/j.urology.2017.02.034

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Radical prostatectomy restores detrusor contraction pattern according to pressure flow parameters2017

    • Author(s)
      Kitta Takeya、Kanno Yukiko、Chiba Hiroki、Moriya Kimihiko、Maruyama Satoru、Abe Takashige、Shinohara Nobuo
    • Journal Title

      Int J Urol

      Volume: 24 Issue: 4 Pages: 301-307

    • DOI

      10.1111/iju.13295

    • NAID

      120006416002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 小児泌尿器科疾患:後期研修で経験したい手術手技 腎盂形成術2019

    • Author(s)
      守屋仁彦、中村美智子、今 雅史、篠原信雄
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 小児における排尿習慣の確立と脳の性分化2019

    • Author(s)
      守屋仁彦、西村陽子、中村美智子、今 雅史、橘田岳也、荒木敦子、宮下ちひろ、伊藤佐智子、長 和俊、三井貴彦 、村井祥代、岸 玲子、篠原信雄
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 「尿道の再建術を極める:PediatricからGeriatricまで」 尿道下裂症例の長期予後と問題点2019

    • Author(s)
      守屋 仁彦
    • Organizer
      第16回泌尿器科再建再生研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 「尿路形成と再建:成功のカギを探る」 巨大尿管・重複腎盂尿管の再建術2019

    • Author(s)
      守屋 仁彦
    • Organizer
      第28回日本小児泌尿器科学会総会・学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 尿道狭窄に対する尿道形成術の経験2019

    • Author(s)
      守屋仁彦、中村美智子、今 雅史、岩原直也、古御堂純、平田由梨絵、坪内 駿、篠原信雄
    • Organizer
      第28回日本泌尿器科学会東部総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Bladder Control and Behavioral Sexual Dimorphism in Children2019

    • Author(s)
      Kimihiko Moriya, Yoko Nishimura, Michiko Nakamura, Masafumi Kon, Takeya Kitta, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Kazutoshi Cho, Takahiko Mitsui, Sachiyo Murai, Katsuya Nonomura, Reiko Kishi, Nobuo Shinohara
    • Organizer
      2019 AUA/SPU meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Panel 4, Adult Hypospadias Considerations: Cosmetic and Endocrinological Problems in Hypospadias Patients at Puberty2019

    • Author(s)
      Kimihiko Moriya
    • Organizer
      3rd Hypospadias World Congress
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 先天性水腎症のmanagement2018

    • Author(s)
      守屋仁彦、中村美智子、今 雅史、篠原信雄
    • Organizer
      第106 回日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 重複腎盂尿管症例に対する同側性尿管尿管吻合術の経験2018

    • Author(s)
      守屋仁彦、中村美智子、今雅史、西村陽子、菅野由岐子、橘田岳也、篠原信雄
    • Organizer
      第106 回日本泌尿器科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Risk factors affecting post-pubertal high serum follicle-stimulating hormone in patients with a history of hypospadias.2018

    • Author(s)
      Kimihiko Moriya, Michiko Nakamura, Yoko Nishimura, Takeya Kitta, Yukiko Kanno, Masafumi Kon, Nobuo Shinohara.
    • Organizer
      SPU/AUA Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 尿道下裂の基礎と臨床 尿道下裂におけるandrology-fetal andrologyとadult andrologyの狭間にて-2018

    • Author(s)
      守屋仁彦、中村美智子、今 雅史、篠原信雄
    • Organizer
      小児泌尿器科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 腎盂形成術後の再発性水腎症に対するmanagement2018

    • Author(s)
      守屋 仁彦
    • Organizer
      小児泌尿器科学会総会
    • Related Report
      2018 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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