TY - JOUR
T1 - Hypoxia induces the dormant state in oocytes through expression of Foxo3
AU - Shimamoto, So
AU - Nishimura, Yohei
AU - Nagamatsu, Go
AU - Hamada, Norio
AU - Kita, Haruka
AU - Hikabe, Orie
AU - Hamazaki, Nobuhiko
AU - Hayashi, Katsuhiko
N1 - Funding Information:
We thank Y. Ohkwawa for technical assistance with the RNA-seq analysis; K. Kitajima and C. Meno for providing microscopes; K. Nakajima for providing the PB vector; F. Arai for providing the FACS Aria II; S. Lopes for proofreading; and M. Saitou for providing BVSC mice. We also thank the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences for technical assistance. This study was supported in part by Ministry of Education, Culture, Sports, Science, and Technology KAKENHI Grants-in-Aid 17H01395, 18H05544, and 18H05545 (to K.H.) and 18K06261 (to G.N.); Management Expenses Grants of Kyushu University (K.H.); Advanced Computational Scientific Program of Research Institute for Information Technology, Kyushu University; the Uehara Memorial Foundation (K.H.); the Takeda Science Foundation (K.H.); a Hayashi Grant-in-Aid for Basic Medical Research (Kyushu University) (K.H.); and a Japan Society for the Promotion of Science Research Fellowship (N. Hamazaki and S.S.).
Funding Information:
ACKNOWLEDGMENTS. We thank Y. Ohkwawa for technical assistance with the RNA-seq analysis; K. Kitajima and C. Meno for providing microscopes; K. Nakajima for providing the PB vector; F. Arai for providing the FACS Aria II; S. Lopes for proofreading; and M. Saitou for providing BVSC mice. We also thank the Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences for technical assistance. This study was supported in part by Ministry of Education, Culture, Sports, Science, and Technology KAKENHI Grants-in-Aid 17H01395, 18H05544, and 18H05545 (to K.H.) and 18K06261 (to G.N.); Management Expenses Grants of Kyushu University (K.H.); Advanced Computational Scientific Program of Research Institute for Information Technology, Kyushu University; the Uehara Memorial Foundation (K.H.); the Takeda Science Foundation (K.H.); a Hayashi Grant-in-Aid for Basic Medical Research (Kyushu University) (K.H.); and a Japan Society for the Promotion of Science Research Fellowship (N. Hamazaki and S.S.).
Publisher Copyright:
© 2019 National Academy of Sciences. All rights reserved.
PY - 2019/6/18
Y1 - 2019/6/18
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1817223116
DO - 10.1073/pnas.1817223116
M3 - Article
C2 - 31147464
AN - SCOPUS:85067622177
SN - 0027-8424
VL - 116
SP - 12321
EP - 12326
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -