Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice

  1. Mitsunori Matsuo
  2. Jia Yuan
  3. Yeon Sun Kim
  4. Amanda Dewar
  5. Hidetoshi Fujita
  6. Sudhansu K Dey  Is a corresponding author
  7. Xiaofei Sun  Is a corresponding author
  1. Cincinnati Children's Hospital Medical Center, United States
  2. Osaka Institute of Technology, Japan

Abstract

Embryonic diapause is a reproductive strategy in which embryo development and growth is temporarily arrested within the uterus to ensure the survival of neonates and mothers during unfavorable conditions. Pregnancy is reinitiated when conditions become favorable for neonatal survival. The mechanism of how the uterus enters diapause in various species remains unclear. Mice with uterine depletion of Foxa2, a transcription factor, are infertile. In this study, we show that dormant blastocysts are recovered from these mice on day 8 of pregnancy with persistent expression of uterine Msx1, a gene critical to maintaining the uterine quiescent state, suggesting that these mice enter embryonic diapause. Leukemia inhibitory factor (LIF) can resume implantation in these mice. Although estrogen is critical for implantation in progesterone-primed uterus, our current model reveals that FOXA2-independent estrogenic effects are detrimental to sustaining uterine quiescence. Interestingly, P4 and anti-estrogen can prolong uterine quiescence in the absence of FOXA2. Although we find that Msx1 expression persists in the uterus deficient in Foxa2, the complex relationship of FOXA2 with Msx genes and estrogen receptors remains to be explored.

Data availability

All data are included in the manuscript.

Article and author information

Author details

  1. Mitsunori Matsuo

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jia Yuan

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yeon Sun Kim

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amanda Dewar

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Hidetoshi Fujita

    Department of Biomedical Engineering, Osaka Institute of Technology, Osaka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Sudhansu K Dey

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    For correspondence
    sk.dey@cchmc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9159-186X
  7. Xiaofei Sun

    Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, United States
    For correspondence
    xiaofei.sun@cchmc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9601-5423

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD103475)

  • Sudhansu K Dey

Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD068524)

  • Sudhansu K Dey

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wei Yan, University of California, Los Angeles, United States

Version history

  1. Received: February 28, 2022
  2. Preprint posted: March 17, 2022 (view preprint)
  3. Accepted: July 20, 2022
  4. Accepted Manuscript published: July 21, 2022 (version 1)
  5. Version of Record published: August 5, 2022 (version 2)

Copyright

© 2022, Matsuo et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mitsunori Matsuo
  2. Jia Yuan
  3. Yeon Sun Kim
  4. Amanda Dewar
  5. Hidetoshi Fujita
  6. Sudhansu K Dey
  7. Xiaofei Sun
(2022)
Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
eLife 11:e78277.
https://doi.org/10.7554/eLife.78277

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https://doi.org/10.7554/eLife.78277

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