Study for the molecular mechanism in an oocyte aging

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293364
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Akutsu Hidenori 国立研究開発法人国立成育医療研究センター, その他部局等, その他 (50347225)
• Co-Investigator(Kenkyū-buntansha): 菅沼 亮太 福島県立医科大学, 医学部, 講師 (30528211) ; 浜谷 敏生 慶應義塾大学, 医学部, 講師 (60265882)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 生殖医学 / 受精卵 / 不育症 / 女性医学

Outline of Final Research Achievements

An oocyte aging is strongly related with impairing totipotency of zygote and X-chromosome inactivation of female embryos is partially key molecule feature on acquiring totipotency. We aimed to explore molecular mechanism on X-chromosome inactivation process in preimplantation development using mice model. An our first accomplishment showed that histone 3 lysine 9 tri-methylation (H3K9me3) was involved in Xm (maternal X-chromosome)-Xist derepression from early preimplantation phases. We also found that the chromatin state at the Xist genomic locus became markedly condensed as oocyte growth proceeded. Xm-Xist was derepressed by chromatin alterations, the derepression was stably maintained and rescued paternal Xist mutational lethality, indicating that loss of Xm-Xist imprinting was irreversible. We propose that chromatin condensation and fine-tuning of Rnf12 dosage are crucial for Xist imprint maintenance by silencing Xm-Xist (Fukda, et al. Plos genetics 2016).

Free Research Field

幹細胞生物学