Long-term influence of the stress exposure in early life on the sexual function in adulthood

• Project/Area Number: 18K09264
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokushima
• Principal Investigator: 松崎 利也 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (70294692)
• Co-Investigator(Kenkyū-buntansha): 苛原 稔 徳島大学, 大学院医歯薬学研究部(医学域), 研究部長 (20160070) ; 岩佐 武 徳島大学, 病院, 特任准教授 (00707903)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Discontinued (Fiscal Year 2019)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ストレス / 性機能 / 性成熟 / 性行動 / 視床下部 / GnRH / プロゲステロン受容体 / テストステロン / 出生後早期のストレス / 長期的影響

Outline of Annual Research Achievements

2019年度は、生後早期に受けた免疫ストレスが成長後の雌ラットの性行動に及ぼす影響につき検討した。生後早期のSD系雌ラットを、control群、PND10LPS群、PND25LPS群に分け、PND10LPS群は日齢10日に、PND25LPS群は日齢25日にLPS(100μg/kg) を腹腔内に投与した。性成熟の指標として日齢28～38日に腟開口(VO)を観察し、生後8週から10週に性周期を観察した。9週齢で卵巣を摘出し、11週齢で性行動と視床下部生殖関連因子のmRNA発現を検討した。PND10LPS群のVO日はcontrol群よりも遅く性周期は長かった。VO日の体重は3群間で差がなかった。LPS投与群の性行動は減弱していた:①パートナー雄のmountおよび雌のlordosisは、PND10LPS群とPND25LPS群がcontrol群よりも少なかった。②求交尾性:ear wigglingはPND10LPS群が、control群およびPND25LPS群よりも少なく、hops/dartsはPND10LPS群がcontrol群よりも少なかった。③受容性:lordosis quotient（LQ）はPND10LPS群がcontrol群よりも低かった。lordosis rating（LR）はPND10LPS群がcontrol群よりも低かった。プロゲステロン受容体(PR) BmRNA発現量は、PND10LPS群がcontrolよりも低く、PR A+B mRNA発現量は、PND10LPS群およびPND25LPS群がcontrolよりも低かった。 GnRH、OTのmRNA発現量は、PND25LPS群が他の２群よりも低かった。生後早期の免疫ストレスは成長後の雌ラットの性行動を減弱させ、この現象は、視床下部PRの恒常的な発現低下に基づくプロゲステロン作用の減弱によるものと示唆された。

Research Products

• [Journal Article] Activin effects on follicular growth in <i>in vitro</i> preantral follicle culture (2019)
  • Author(s): Tanaka Yu、Matsuzaki Toshiya、Tanaka Naoko、Iwasa Takeshi、Kuwahara Akira、Irahara Minoru
  • Journal Title: The Journal of Medical Investigation Volume: 66 Issue: 1.2 Pages: 165-171
  • DOI: 10.2152/jmi.66.165
  • NAID: 130007638770
  • ISSN: 1343-1420, 1349-6867
  • Year and Date: 2019-02-15
  • Peer Reviewed
• [Journal Article] The effects of chronic oxytocin administration on body weight and food intake in DHT-induced PCOS model rats (2019)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Mayila Yiliyasi、Kawakita Takako、Yanagihara Rie、Irahara Minoru
  • Journal Title: Gynecological Endocrinology Volume: 36 Issue: 1 Pages: 55-60
  • DOI: 10.1080/09513590.2019.1631276
  • Peer Reviewed
• [Journal Article] Oxytocin treatment reduced food intake and body fat and ameliorated obesity in ovariectomized female rats (2019)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Mayila Yiliyasi、Yanagihara Rie、Yamamoto Yuri、Kawakita Takako、Kuwahara Akira、Irahara Minoru
  • Journal Title: Neuropeptides Volume: 印刷中 Pages: 49-57
  • DOI: 10.1016/j.npep.2019.03.002
  • Peer Reviewed
• [Journal Article] Neurokinin B receptor agonist and Dynorphin receptor antagonist stimulated luteinizing hormone secretion in fasted male rodents (2018)
  • Author(s): Matsuzaki Toshiya、Tungalagsuvd Altankhuu、Munkhzaya Munkhsaikhan、Iwasa Takeshi、Yano Kiyohito、Mayila Yiliyasi、Tokui Takako、Yanagihara Rie、Matsui Sumika、Kato Takeshi、Kuwahara Akira、Irahara Minoru
  • Journal Title: Endocrine Journal Volume: 65 Issue: 4 Pages: 485-492
  • DOI: 10.1507/endocrj.EJ17-0136
  • NAID: 130006727048
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Effects of chronic testosterone administration on the degree of preference for a high-fat diet and body weight in gonadal-intact and ovariectomized female rats (2018)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Yano Kiyohito、Yiliyasi Mayila、Kuwahara Akira、Matsui Sumika、Irahara Minoru
  • Journal Title: Behavioural Brain Research Volume: 349 Pages: 102-108
  • DOI: 10.1016/j.bbr.2018.02.021
  • NAID: 120006844028
  • Peer Reviewed
• [Journal Article] Prenatal undernutrition decreases the anorectic response to septic doses of lipopolysaccharides in adulthood in male rats (2018)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Yano Kiyohito、Mayila Yiliyasi、Irahara Minoru
  • Journal Title: International Journal of Developmental Neuroscience Volume: 69 Issue: 1 Pages: 39-43
  • DOI: 10.1016/j.ijdevneu.2018.06.010
  • Peer Reviewed
• [Journal Article] Effects of Low Energy Availability on Reproductive Functions and Their Underlying Neuroendocrine Mechanisms (2018)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Yano Kiyohito、Mayila Yiliyasi、Yanagihara Rie、Yamamoto Yuri、Kuwahara Akira、Irahara Minoru
  • Journal Title: Journal of Clinical Medicine Volume: 7 Issue: 7 Pages: 166-166
  • DOI: 10.3390/jcm7070166
  • Peer Reviewed
• [Journal Article] 11-oxygenated C19 steroids as circulating androgens in women with polycystic ovary syndrome (2018)
  • Author(s): Yoshida T, Matsuzaki T, Miyado M, Saito K, Iwasa T, Matsubara Y, Ogata T, Irahara M, Fukami M.
  • Journal Title: Endocrine Journal Volume: 65 Issue: 10 Pages: 979-990
  • DOI: 10.1507/endocrj.EJ18-0212
  • NAID: 130007501323
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women (2018)
  • Author(s): Matsuzaki Toshiya、Iwasa Takeshi、Yanagihara Rie、Komasaka Mizuki、Yano Kiyohito、Mayila Yiliyasi、Tachibana Ayaka、Yamamoto Yuri、Kato Takeshi、Kuwahara Akira、Irahara Minoru
  • Journal Title: Reproductive Medicine and Biology Volume: 17 Issue: 3 Pages: 315-324
  • DOI: 10.1002/rmb2.12208
  • NAID: 120007141573
  • Peer Reviewed
• [Journal Article] Pregnancy outcomes of women who received conservative therapy for endometrial carcinoma or atypical endometrial hyperplasia (2018)
  • Author(s): Matsuzaki Toshiya、Iwasa Takeshi、Kawakita Takako、Yamamoto Yuri、Abe Akiko、Hayashi Aki、Yano Kiyohito、Nishimura Masato、Kuwahara Akira、Irahara Minoru
  • Journal Title: Reproductive Medicine and Biology Volume: 17 Issue: 3 Pages: 325-328
  • DOI: 10.1002/rmb2.12209
  • NAID: 120007141572
  • Peer Reviewed
• [Journal Article] Prenatal undernutrition attenuates fasting-induced reproductive dysfunction in pre-pubertal male rats (2018)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Yano Kiyohito、Mayila Yiliyasi、Irahara Minoru
  • Journal Title: International Journal of Developmental Neuroscience Volume: 71 Issue: 1 Pages: 30-33
  • DOI: 10.1016/j.ijdevneu.2018.07.005
  • Peer Reviewed
• [Journal Article] Prenatal undernutrition affects the phenotypes of PCOS model rats (2018)
  • Author(s): Iwasa Takeshi、Matsuzaki Toshiya、Yano Kiyohito、Mayila Yiliyasi、Yanagihara Rie、Yamamoto Yuri、Kuwahara Akira、Irahara Minoru
  • Journal Title: Journal of Endocrinology Volume: 239 Issue: 2 Pages: 137-151
  • DOI: 10.1530/joe-18-0335
  • Peer Reviewed
• [Journal Article] Prenatal undernutrition suppresses sexual behavior in female rats (2018)
  • Author(s): Matsuzaki Toshiya、Munkhzaya Munkhsaikhan、Iwasa Takeshi、Tungalagsuvd Altankhuu、Yano Kiyohito、Mayila Yiliyasi、Yanagihara Rie、Tokui Takako、Kato Takeshi、Kuwahara Akira、Matsui Sumika、Irahara Minoru
  • Journal Title: General and Comparative Endocrinology Volume: 269 Pages: 46-52
  • DOI: 10.1016/j.ygcen.2018.08.013
  • Peer Reviewed
• [Journal Article] The reduction in sexual behavior induced by neonatal immune stress is not related to androgen levels in male rats (2018)
  • Author(s): Mayila Yiliyasi、Matsuzaki Toshiya、Iwasa Takeshi、Tungalagsuvd Altankhuu、Munkhzaya Munksaihan、Yano Kiyohito、Yanagihara Rie、Tokui Takako、Kato Takeshi、Kuwahara Akira、Irahara Minoru
  • Journal Title: International Journal of Developmental Neuroscience Volume: 71 Issue: 1 Pages: 163-171
  • DOI: 10.1016/j.ijdevneu.2018.08.003
  • Peer Reviewed
• [Presentation] The reduction of sexual behavior in adult female rats exposed to immune stress in neonatal period was associated with reduced expression of progesterone receptors in hypothalamus (2019)
  • Author(s): Toshiya Matsuzaki, Yiliyasi Mayila, Takeshi Iwasa, Kiyohito Yano, Rie Yanagihara and Minoru Irahara.
  • Organizer: 第71回日本産科婦人科学会学術講演会
• [Presentation] シンポジウム：排卵障害動物モデルを用いたゴナドトロピン分泌異常に関する検討 (2019)
  • Author(s): 松崎 利也
  • Organizer: 日本下垂体研究会 第34回学術集会
• [Presentation] Efficacy of individualized dose of FSH in ovarian stimulation for unexplained sterility. (2018)
  • Author(s): Toshiya Matsuzaki, Rie Yanagihara, Kiyohito Yano, Takeshi Iwasa, Minoru Irahara.
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] The effects of chronic testosterone administration on body weight, food intake, and fat weight were changed age-dependently. (2018)
  • Author(s): Takeshi Iwasa, Toshiya Matsuzaki, Rie Yanagihara, Mayila Yiliyasi, Kiyohito Yano, Minoru Irahara.
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] The influence of early life psychological stress on sexual maturation and on sexual activity in female rats. (2018)
  • Author(s): Kiyohito Yano, Toshiya Matsuzaki, Rie Yanagihara, Mayila Yiliyasi, Takeshi Iwasa, Minoru Irahra.
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] Individualized initial dose in low-dose FSH therapy for WHO group 2 patients. (2018)
  • Author(s): Rie Yanagihara, Toshiya Matsuzaki, Takeshi Iwasa, Kiyohito Yano, Minoru Irahara.
  • Organizer: 第70回日本産科婦人科学会学術講演会
• [Presentation] ランチョンセミナー：排卵誘発におけるFSH製剤の安全な使い方 (2018)
  • Author(s): 松崎利也
  • Organizer: 第70回日本産科婦人科学会学術講演会
  • Invited
• [Presentation] 新しいプロトコールによるFSH低用量漸増療法の排卵誘発治療における効果と安全性の検討 (2018)
  • Author(s): 松崎利也、柳原里江、岩佐 武、Mayila Yiliyasi、山本由理、桑原 章、苛原 稔
  • Organizer: 第71回中国四国産科婦人科学会総会ならびに学術講演会