2023 Fiscal Year Final Research Report

Oviduct as the site of fertilization and early embryonic development: Verification of its physiological functions using genetically engineering hamster model for clinical application

Research Project

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Project/Area Number	18KK0256
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
Research Institution	Nihon University (2022-2023) Juntendo University (2018-2021)
Principal Investigator	ARAKI Yoshihiko 日本大学, 医学部, 客員教授 (70250933)
Co-Investigator(Kenkyū-buntansha)	小倉淳郎国立研究開発法人理化学研究所, バイオリソース研究センター, 室長 (20194524) 眞貝洋一国立研究開発法人理化学研究所, 開拓研究本部, 主任研究員 (20211972) 藤原浩金沢大学, 医学系, 教授 (30252456) 鏡京介金沢大学, 附属病院, 講師 (80748616)
Project Period (FY)	2018-10-09 – 2024-03-31
Keywords	哺乳類 / 卵管 / ハムスター / 遺伝子編集 / 受精 / 着床 / 初期胚発生
Outline of Final Research Achievements	The oviductal lumen is a specialized chamber that provides an environment that strictly regulates fertilization and early embryogenesis, but the regulatory mechanisms to gametes and zygotes are unclear. We evaluated the oviductal regulation of early embryonic development using Ovgp1-knockout (KO) golden hamsters. The experimental results revealed the following: (1) female Ovgp1-KO failed to produce litters; (2) in the oviducts of Ovgp1-KO, fertilized eggs were sometimes identified, but their morphology showed abnormal features; (3) the number of implantations in the Ovgp1-KO was low; (4) even if implantations occurred, the embryos developed abnormally and eventually died; and (5) Ovgp1-KO female ovaries transferred to wild-type females resulted in the production of Ovgp1-KO egg-derived OVGP1-null litters, but the reverse experiment did not. This animal model shows that the fate of the zygote is determined not only genetically, but also by the surrounding oviductal microenvironment.
Free Research Field	生殖生物学
Academic Significance and Societal Importance of the Research Achievements	本研究の結果はマウス同様に極めて繁殖力の高いハムスターでは、in vivoでその胚初期発生にOVGP1を介した極めて重要な生理的イベントが卵管内で行われていることを示した。即ち、受精卵（分化全能性細胞）の運命は遺伝的に決まるだけではなく、着床までの卵管微小環境が正常な発育のために極めて大きな意味を持つことを強く示唆する動物モデルを世界で初めて樹立した。受精直後の哺乳類初期胚発生における微小環境の意味を分子レベルで理解する上で、今後この動物モデルを用いて基礎・臨床的に重要な知見を得る可能性が大いに期待される。