Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
- Cincinnati Children's Hospital Medical Center, United States
- 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.
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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.
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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Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
eLife 11:e78277.
https://doi.org/10.7554/eLife.78277
