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Central mechanism regulating reproduction in mammals under heat stress

Research Project

Project/Area Number 20H03127
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42010:Animal production science-related
Research InstitutionNagoya University

Principal Investigator

Uenoyama Yoshihisa  名古屋大学, 生命農学研究科, 准教授 (70324382)

Co-Investigator(Kenkyū-buntansha) 平林 真澄  生理学研究所, 行動・代謝分子解析センター, 准教授 (20353435)
中村 翔  名古屋大学, アジアサテライトキャンパス学院(農), 特任准教授 (50829223)
井上 直子  名古屋大学, 生命農学研究科, 准教授 (90377789)
森田 康広  帯広畜産大学, 畜産学部, 准教授 (90818262)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2022: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Keywords暑熱ストレス / 繁殖成績 / ウシ / ラット / 繁殖促進技術
Outline of Research at the Start

本研究の目的は、暑熱環境下において家畜の繁殖成績の低下を招く脳内メカニズムを解明し、地球温暖化により頻発する家畜の生産性低下を克服するための知見を集積することである。本研究では、体温上昇を感知する脳内の熱センシング細胞 (脳熱センサー) を着想し、熱センシング細胞が繁殖を司るキスペプチンニューロンを抑制するメカニズムを明らかにする。さらに、熱センシング細胞が分泌するシグナル分子の拮抗剤により暑熱環境下における家畜の繁殖機能低下を克服できることを検証する。本知見により、新たな家畜の繁殖促進技術の開発を可能とし、家畜の繁殖成績の向上を通じて畜産物の生産性の革新的な向上に資することが期待できる。

Outline of Final Research Achievements

This study aimed to elucidate the brain mechanism that decreased reproductive performance in mammals under heat stress and to accumulate knowledge to overcome the decline in livestock productivity. To this end, the central mechanisms suppressing gonadotropin-releasing hormone (GnRH)/luteinizing hormone (LH) secretion by undernutrition and lactation were investigated using rats as an animal model. The results showed that kisspeptin neurons located in the hypothalamic arcuate nucleus serve as the GnRH pulse generator, which controls the follicular development in female mammals, and that central endogenous opioid peptides mediate the suppression of GnRH/LH secretion by undernutrition and lactation.

Academic Significance and Societal Importance of the Research Achievements

50年来の謎であった性腺刺激ホルモン放出ホルモン (GnRH) のパルス分泌を制御するGnRHパルス発生機構の本体にを明らかにしたという学術的な意義に加え、夏季の猛暑下における家畜の繁殖障害を克服に資する知見を集積し、内因性オピオイドペプチドの拮抗剤が新規な家畜の繁殖促進剤のシーズとなるという社会的に大きな意義をもつ成果を得た。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (43 results)

All 2024 2023 2022 2021 2020 Other

All Journal Article (22 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 21 results,  Open Access: 17 results) Presentation (18 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (3 results)

  • [Journal Article] Raphe glucose-sensing serotonergic neurons stimulate KNDy neurons to enhance LH pulses via 5HT2CR: rat and goat studies2024

    • Author(s)
      Nakamura, S., Sasaki, T., Uenoyama, Y., Inoue, N., Nakanishi, M., Yamada, K., Morishima, A., Suzumura, R., Kitagawa, Y., Morita, Y., Ohkura, S. and Tsukamura, H.
    • Journal Title

      Scientific Reports

      Volume: - Issue: 1

    • DOI

      10.1038/s41598-024-58470-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neonatal Aromatase Inhibition Blocked Defeminization of AVPV <i>Kiss1</i> Neurons and LH Surge-Generating System in Male Rats2024

    • Author(s)
      Yamada Koki、Mano Tetsuya、Hazim Safiullah、Takizawa Marina、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Endocrinology

      Volume: 165 Issue: 4

    • DOI

      10.1210/endocr/bqae028

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Capturing temperature changes on the ocular surface along with estrus and ovulation using infrared thermography in Japanese Black cows2024

    • Author(s)
      Riho OZAKI, Seiji INOUE, Yuki YOROZUI, Rei ICHIKAWA, Naoki YAMADA, Seiya HIGASHI, Shuichi MATSUYAMA, Hiroko TSUKAMURA, Satoshi OHKURA, Yoshihisa UENOYAMA, Yasuhiro MORITA
    • Journal Title

      Journal of Reproduction and Development

      Volume: 70 Issue: 1 Pages: 49-54

    • DOI

      10.1262/jrd.2022-116

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conditional Oprk1-dependent Kiss1 deletion in kisspeptin neurons caused estrogen-dependent LH pulse disruption and LH surge attenuation in female rats2023

    • Author(s)
      Nagae Mayuko、Yamada Koki、Enomoto Yuki、Kometani Mari、Tsuchida Hitomi、Panthee Arvinda、Nonogaki Miku、Matsunaga Nao、Takizawa Marina、Matsuzaki Sena、Hirabayashi Masumi、Inoue Naoko、Tsukamura Hiroko、Uenoyama Yoshihisa
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 20495-20495

    • DOI

      10.1038/s41598-023-47222-5

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sex difference in developmental changes in visualized <i>Kiss1</i> neurons in newly generated <i>Kiss1-Cre</i> rats2023

    • Author(s)
      YAMADA Koki、NAGAE Mayuko、MANO Tetsuya、TSUCHIDA Hitomi、HAZIM Safiullah、GOTO Teppei、SANBO Makoto、HIRABAYASHI Masumi、INOUE Naoko、UENOYAMA Yoshihisa、TSUKAMURA Hiroko
    • Journal Title

      Journal of Reproduction and Development

      Volume: 69 Issue: 5 Pages: 227-238

    • DOI

      10.1262/jrd.2023-019

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enkephalin-δ opioid receptor signaling partly mediates suppression of LH release during early lactation in rats2023

    • Author(s)
      TSUCHIDA Hitomi、TAKIZAWA Marina、NONOGAKI Miku、INOUE Naoko、UENOYAMA Yoshihisa、TSUKAMURA Hiroko
    • Journal Title

      Journal of Reproduction and Development

      Volume: 69 Issue: 4 Pages: 192-197

    • DOI

      10.1262/jrd.2023-006

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2023 Annual Research Report
  • [Journal Article] Kisspeptin and lactational anestrus: Current understanding and future prospects2023

    • Author(s)
      Uenoyama Yoshihisa、Inoue Naoko、Tsukamura Hiroko
    • Journal Title

      Peptides

      Volume: 166 Pages: 171026-171026

    • DOI

      10.1016/j.peptides.2023.171026

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <scp>KNDy</scp> neurones and <scp>GnRH</scp>/<scp>LH</scp> pulse generation: Current understanding and future aspects2023

    • Author(s)
      Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Journal of Neuroendocrinology

      Volume: 35 Issue: 9

    • DOI

      10.1111/jne.13285

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enkephalin-δ opioid receptor signaling mediates glucoprivic suppression of LH pulse and gluconeogenesis in female rats2023

    • Author(s)
      Tsuchida Hitomi、Nonogaki Miku、Takizawa Marina、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Endocrinology

      Volume: 164 Issue: 3

    • DOI

      10.1210/endocr/bqac216

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hindbrain adenosine 5-triphosphate (ATP)-purinergic signaling triggers LH surge and ovulation via activation of AVPV kisspeptin neurons in rats2023

    • Author(s)
      Inoue Naoko、Hazim Safiullah、Tsuchida Hitomi、Dohi Yuri、Ishigaki Ren、Takahashi Ai、Otsuka Yuki、Yamada Koki、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      The Journal of Neuroscience

      Volume: 43 Issue: 12 Pages: 2140-2152

    • DOI

      10.1523/jneurosci.1496-22.2023

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dynorphin-κ-opioid receptor signaling, but not μ-opioid receptor signaling, partly mediates the suppression of luteinizing hormone release during late lactation in rats2022

    • Author(s)
      Tsuchida Hitomi、Nonogaki Miku、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Neuroscience Letters

      Volume: 791 Pages: 136920-136920

    • DOI

      10.1016/j.neulet.2022.136920

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Opioidergic pathways and kisspeptin in the regulation of female reproduction in mammals2022

    • Author(s)
      Uenoyama Yoshihisa、Tsuchida Hitomi、Nagae Mayuko、Inoue Naoko、Tsukamura Hiroko
    • Journal Title

      Frontiers in Neuroscience2022

      Volume: 16

    • DOI

      10.3389/fnins.2022.958377

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular and molecular mechanisms regulating the KNDy neuronal activities to generate and modulate GnRH pulse in mammals2022

    • Author(s)
      Ikegami Kana、Watanabe Youki、Nakamura Sho、Goto Teppei、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Frontiers in Neuroendocrinology

      Volume: 64 Pages: 100968-100968

    • DOI

      10.1016/j.yfrne.2021.100968

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kisspeptin neurons as a key player bridging the endocrine system and sexual behavior in mammals2022

    • Author(s)
      Nakamura Sho、Watanabe Youki、Goto Teppei、Ikegami Kana、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Frontiers in Neuroendocrinology

      Volume: 64 Pages: 100952-100952

    • DOI

      10.1016/j.yfrne.2021.100952

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of embryo transfer in the musk shrew (<i>Suncus murinus</i>)2022

    • Author(s)
      INOUE Naoko、HOTTA Akinori、GOTO Teppei、HIRABAYASHI Masumi、UENOYAMA Yoshihisa、TSUKAMURA Hiroko
    • Journal Title

      Journal of Reproduction and Development

      Volume: 68 Issue: 5 Pages: 340-344

    • DOI

      10.1262/jrd.2022-003

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of Tfap2c‐T2A‐tdTomato knock‐in reporter rats via adeno‐associated virus‐mediated efficient gene targeting2022

    • Author(s)
      Oikawa Mami、Nagae Mayuko、Mizuno Naoaki、Iwatsuki Kenyu、Yoshida Fumika、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko、Nakauchi Hiromitsu、Hirabayashi Masumi、Kobayashi Toshihiro
    • Journal Title

      Molecular Reproduction and Development

      Volume: 89 Issue: 3 Pages: 129-132

    • DOI

      10.1002/mrd.23562

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Central somatostatin-somatostatin receptor 2 signaling mediates lactational suppression of luteinizing hormone release via the inhibition of glutamatergic interneurons during late lactation in rats2022

    • Author(s)
      Sugimoto Arisa, Tsuchida Hitomi, Nagae Mayuko, Inoue Naoko, Uenoyama Yoshihisa, Tsukamura Hiroko
    • Journal Title

      Journal of Reproduction and Development

      Volume: 68 Issue: 3 Pages: 190-197

    • DOI

      10.1262/jrd.2022-009

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Central μ-Opioid Receptor Antagonism Blocks Glucoprivic LH Pulse Suppression and Gluconeogenesis/Feeding in Female Rats2021

    • Author(s)
      Tsuchida Hitomi、Kawai Narumi、Yamada Koki、Takizawa Marina、Inoue Naoko、Uenoyama Yoshihisa、Tsukamura Hiroko
    • Journal Title

      Endocrinology

      Volume: 162 Issue: 10 Pages: 1-12

    • DOI

      10.1210/endocr/bqab140

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kisspeptin Neurons and Estrogen?Estrogen Receptor α Signaling: Unraveling the Mystery of Steroid Feedback System Regulating Mammalian Reproduction2021

    • Author(s)
      Uenoyama Yoshihisa、Inoue Naoko、Nakamura Sho、Tsukamura Hiroko
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 17 Pages: 9229-9229

    • DOI

      10.3390/ijms22179229

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of KNDy neurons expressing kisspeptin, neurokinin B, and dynorphin A as a GnRH pulse generator controlling mammalian reproduction.2021

    • Author(s)
      Uenoyama Y, Nagae M, Tsuchida H, Inoue N, Tsukamura H.
    • Journal Title

      Frontiers in Endocrinology.

      Volume: 12 Pages: 1-12

    • DOI

      10.3389/fendo.2021.724632

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct evidence that KNDy neurons maintain gonadotropin pulses and folliculogenesis as the GnRH pulse generator2021

    • Author(s)
      Nagae Mayuko、Uenoyama Yoshihisa、Okamoto Saki、Tsuchida Hitomi、Ikegami Kana、Goto Teppei、Majarune Sutisa、Nakamura Sho、Sanbo Makoto、Hirabayashi Masumi、Kobayashi Kenta、Inoue Naoko、Tsukamura Hiroko
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 5

    • DOI

      10.1073/pnas.2009156118

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paraventricular dynorphin A neurons mediate LH pulse suppression induced by hindbrain glucoprivation in female rats.2020

    • Author(s)
      Hitomi Tsuchida, Parvin Mostari, Koki Yamada, Sae Miyazaki, Yuki Enomoto, Naoko Inoue, Yoshihisa Uenoyama, Hiroko Tsukamura.
    • Journal Title

      Endocrinology

      Volume: 161(11) Issue: 11 Pages: 1-18

    • DOI

      10.1210/endocr/bqaa161

    • NAID

      120007192020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Presentation] "KNDy neurons as the GnRH pulse generator: Twenty percent of KNDy neurons are enough to maintain gonadotropin pulse and folliculogenesis "2021

    • Author(s)
      Yoshihisa UENOYAMA
    • Organizer
      Kisspeptin Virtual Conference
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] β-エンドルフィン-μ-オピオイド受容体シグナリングはグルコース利用阻害による生殖機能抑制を仲介する2021

    • Author(s)
      土田仁美, 河合成美、井上直子, 上野山賀久, 束村博子
    • Organizer
      第94回日本内分泌学会学術総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 室傍核ダイノルフィンAニューロンは泌乳ラットにおけるLHパルス抑制を仲介する2021

    • Author(s)
      土田仁美, 井上直子, 上野山賀久, 束村博子
    • Organizer
      第114回日本繁殖生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] GnRH パルスジェネレーター解析のための新規 Cre 発現ラットの作製2021

    • Author(s)
      長江麻佑子、小林俊寛、三宝誠、平林真澄、水野直彬、中内啓光、榎本悠希、井上直子、束村博子、上野山賀久
    • Organizer
      第114回日本繁殖生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 雌ラットキスペプチンニューロンにおけるSNAP-25遺伝子の発現解析2021

    • Author(s)
      山田晃熙、井上直子、上野山賀久、束村博子
    • Organizer
      第114回日本繁殖生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 泌乳ラットにおけるKiss1発現抑制を担うエストロゲン受容体共役コリプレッサーの探索2021

    • Author(s)
      滝沢麻里奈, 井上直子, 上野山賀久, 束村博子
    • Organizer
      第114回日本繁殖生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Search for purinergic neurons projecting to the vicinity of the kisspeptin neurons in the anteroventral periventricular nucleus by retrograde tracing2021

    • Author(s)
      Safiullah HAZIM, Yoshihisa UENOYAMA, Hiroko TSUKAMURA, Naoko INOUE
    • Organizer
      第114回日本繁殖生物学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 性成熟を制御する弓状核KNDyニューロン2021

    • Author(s)
      上野山賀久、井上直子、束村博子
    • Organizer
      第54回日本小児内分泌学会学術集会@札幌コンベンションセンター
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脳内β-エンドルフィン-μ-オピオイド受容体シグナリングがグルコース利用阻害によるLH分泌抑制/糖新生/摂食誘起を仲介する2021

    • Author(s)
      土田仁美, 井上直子, 上野山賀久, 束村博子
    • Organizer
      第45回日本比較内分泌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 卵胞発育を司るGnRHパルス発生機構の同定2021

    • Author(s)
      長江麻佑子、土田仁美、井上直子、束村博子、上野山賀久
    • Organizer
      第45回日本比較内分泌学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] β-エンドルフィン-μ-オピオイド受容体シグナリングは低栄養による生殖機能抑制と糖新生/摂食の誘起を仲介する2021

    • Author(s)
      土田仁美, 井上直子, 上野山賀久, 束村博子
    • Organizer
      第16回 GPCR研究会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 遺伝子改変ラットを用いた哺乳類の卵胞発育中枢の同定2021

    • Author(s)
      土田仁美, 井上直子, 上野山賀久, 束村博子
    • Organizer
      愛知県農学系4機関による研究交流会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 室傍核ダイノルフィンニューロンは泌乳ラットにおけるLHパルスの抑制を仲介する2021

    • Author(s)
      土田仁美, 井上直子, 上野山賀久, 束村博子
    • Organizer
      第26回日本生殖内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Kiss1細胞常時可視化遺伝子改変ラットを用いた雌雄脳内Kiss1細胞分布の経時的解析2021

    • Author(s)
      山田晃熙、長江麻佑子、眞野哲也、井上直子、上野山賀久、平林真澄、束村博子
    • Organizer
      第26回日本生殖内分泌学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] KNDyニューロン復元によるゴナドトロピン放出ホルモン (GnRH) パルスと卵胞発育の回復2020

    • Author(s)
      上野山賀久、長江麻佑子、岡本沙季、土田仁美、井上直子、束村博子
    • Organizer
      日本畜産学会第128回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 室傍核ダイノルフィンニューロンがグルコース利用阻害による生殖機能抑制を仲介する2020

    • Author(s)
      土田 仁美,井上 直子,上野山 賀久,束村 博子
    • Organizer
      第25回日本生殖内分泌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 弓状核特異的Kiss1レスキュー/ノックアウトラットを用いたGnRHパルスジェネレーターの同定2020

    • Author(s)
      長江麻佑子、上野山賀久、岡本沙季、土田仁美、池上花奈、後藤哲平、三宝誠、平林真澄、小林憲太、井上直子、束村博子
    • Organizer
      第25回日本生殖内分泌学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 低栄養による生殖機能抑制は室傍核ダイノルフィンニューロンによる弓状核キスペプチンニューロンの抑制によって仲介される2020

    • Author(s)
      土田 仁美,井上 直子,上野山 賀久,束村 博子
    • Organizer
      第113回日本繁殖生物学会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 先天的不妊モデル動物の繁殖能力の回復に成功-卵胞発育を司る繁殖中枢ニューロンを同定-

    • URL

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Published: 2020-04-28   Modified: 2025-01-30  

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