Hypoxia induces the dormant state in oocytes through expression of Foxo3

So Shimamoto, Yohei Nishimura, Go Nagamatsu, Norio Hamada, Haruka Kita, Orie Hikabe, Nobuhiko Hamazaki, Katsuhiko Hayashi

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Abstract

In mammals, most immature oocytes remain dormant in the primordial follicles to ensure the longevity of female reproductive life. A precise understanding of mechanisms underlying the dormancy is important for reproductive biology and medicine. In this study, by comparing mouse oogenesis in vivo and in vitro, the latter of which bypasses the primordial follicle stage, we defined the gene-expression profile representing the dormant state of oocytes. Overexpression of constitutively active FOXO3 partially reproduced the dormant state in vitro. Based on further gene-expression analysis, we found that a hypoxic condition efficiently induced the dormant state in vitro. The effect of hypoxia was severely diminished by disruption of the Foxo3 gene and inhibition of hypoxia-inducible factors. Our findings provide insights into the importance of environmental conditions and their effectors for establishing the dormant state.

Original languageEnglish
Pages (from-to)12321-12326
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number25
DOIs
Publication statusPublished - Jun 18 2019

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