Clarify mechanism for lactational or aged infertility depending on newly discovered GPR61 in bovine gonadotroph

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02329
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42010:Animal production science-related
• Research Institution: Yamaguchi University
• Principal Investigator: Kadokawa Hiroya 山口大学, 共同獣医学部, 教授 (80370592)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 加齢 / 泌乳

Outline of Final Research Achievements

The details of studies were published in Scientific Reports in 2021. The background of the study is infertility caused by suppressed functions of the central player of fertility control, gonadotrophs in pituitaries, dues to lactation stress and aging via unclarified mechanisms in cattle. This study clarified an important pathophysiological mechanism in brain, and causative substance, ethanolamine plasmalogen (EPl). Both lactation-stress and aging make worse the quality of EPl resulted in weak stimulation function for gonadotrophs. The primary reason of this successful discoveries is G-protein-coupled receptor 61 (GPR61), discovered by Kadokawa et al. in bovine pituitaries. This novel receptor is co- localize with GnRH receptors on the gonadotroph surface. Another reason of this success is utilizing a newly developed method, two-dimensional liquid chromatography-mass spectrometry. The obtained results can be developed also for human medicine.

Free Research Field

繁殖

Academic Significance and Societal Importance of the Research Achievements

分娩後泌乳牛や加齢後雌和牛で生じる繁殖障害の大部分は、下垂体前葉内のゴナドトロフ細胞の異常が原因である。本研究により、未解明であった病理メカニズム、中でも暗黒大陸とされてきた脳内のメカニズムが発見された。現在、日本国内の牛肉生産の現場では、子牛が著しく不足しているため、肉牛農家は経営存続の危機に陥っている。特に繁殖農家では10歳までに８回分娩させる対策が極めて重要になったが、加齢後の雌和牛では、下垂体機能の低下のため不妊個体が多発する。本研究の成果は、これらの問題解決のための重要な基盤になる。これらの発見はヒトにもあてはめられる可能性が高く、産婦人科用等の創薬シーズとして期待される。