Mechanism mediating neonatal estrogen-induced suppression of the reproductive function

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19186
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 42:Veterinary medical science, animal science, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Tsukamura Hiroko 名古屋大学, 生命農学研究科, 教授 (00212051)
• Co-Investigator(Kenkyū-buntansha): 上野山 賀久 名古屋大学, 生命農学研究科, 准教授 (70324382) ; 井上 直子 名古屋大学, 生命農学研究科, 准教授 (90377789)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: キスペプチン / Kiss1 / エストロゲン / テストステロン / 発達脳

Outline of Final Research Achievements

This study examined the mechanism mediating specific and irreversible loss of kisspeptin gene (Kiss1) expression in hypothalamic kisspeptin neurons by neonatal estrogen in the developing brain. The following studies were conducted. (1) We succeeded in creating gene-modified rats in which kisspeptin neurons can be constantly visualized with a fluorescent protein regardless of Kiss1 expression. Furthermore, we histologically examined fluorescent-expressing cells in the brain during various phases of development. (2) We verified the effects of steroid treatment in the developing brain using rats with constantly visible kisspeptin neurons and we found that estrogen aromatized from testosterone in developing male rats reduces the number of kisspeptin neurons in the hypothalamus and causes the dysfunction of the ovulation system in rats.
(3) We obtained a list of genes expressed in hypothalamic kisspeptin neurons distributed in the anterior and posterior hypothalamus.

Free Research Field

家畜繁殖学・神経内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究は、哺乳類において発達脳への性ステロイドホルモン感作が、生涯にわたって生殖機能を抑制するメカニズムの解明を目指しており、家畜における排卵障害や卵胞発育不全の機序の理解に資する点で社会的意義がある。加えて、発達期の性ステロイドホルモンが生殖中枢キスペプチンニューロンのキスペプチン遺伝子発現を抑制するメカニズムの解明を通じで、不可逆な遺伝子発現抑制の分子メカニズムを解明する点で、学術的意義がある。