2021 Fiscal Year Final Research Report

Genetic alteration from in-vitro culture environment in mammalian offspring born through in vitro fertilization

Research Project

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Project/Area Number	19K09787
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	Tokyo Medical University
Principal Investigator	NAOKI KJI 東京医科大学, 医学部, 教授 (80169987)
Co-Investigator(Kenkyū-buntansha)	笹岡俊邦新潟大学, 脳研究所, 教授 (50222005) 阿久津英憲国立研究開発法人国立成育医療研究センター, 生殖医療研究部, 部長 (50347225) 山中紋奈東京医科大学, 医学部, 助教 (60838689)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	マウス / 体外受精 / オクタン酸 / インプリンティング
Outline of Final Research Achievements	The effect of octanoic acid (OA) in the embryo culture medium was investigated. Mouse embryos were cultured in KSOM culture medium containing0.5% w/v of recombinant human albumin, 400 mmM of N-acetyl tryptophan, and 0, 400, and 600 mmM of OA, respectively. The blastocyst development rates were 32/34 (94%), 28/36 (78%), and 28/40 (70%), respectively, significantly decreased with increasing OA concentration. After embryo transfer to pseudo-pregnant female mice, average birth weight of female pup were 1.08 ± 0.06 g, 1.15 ± 0.09 g, and 1.45 ± 0.05 g, tended to increase with increasing OA concentration (p = 0.05 in the 0μM group and 60μM group). However, in males, there was no difference in birth weight due to OA concentration, and there was no significant difference in weight up to 4 weeks after birth both in males and females. It was suggested that exposure to high concentrations of octanoic acid during embryo culture could increase birth weight in females.
Free Research Field	生殖医療
Academic Significance and Societal Importance of the Research Achievements	ヒト体外受精由来出生（凍結胚移植由来）児は自然妊娠児に比較して出生体重が重いことが知られており、体外胚培養によって胚がうける影響についての関心は高いが、影響を来す因子やその遺伝子変化については詳しく解明されてない。ヒト体外受精培養液のほぼすべてに、生理的濃度の1000倍以上のオクタン酸（以下Octanoic Acid、以下OA）が添加されている。我々はOAがマウス胚にとりこまれ、エネルギー代謝に利用されていることを報告している。本研究の成果は、OAがヒト体外培養中に胚に影響する可能性を示唆するとともに、その病因解明のモデル系を提供する可能性がある。