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Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice

Authors :
Mitsunori Matsuo
Jia Yuan
Yeon Sun Kim
Amanda Dewar
Hidetoshi Fujita
Sudhansu K Dey
Xiaofei Sun
Source :
eLife, Vol 11 (2022)
Publication Year :
2022
Publisher :
eLife Sciences Publications Ltd, 2022.

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, progesterone 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.

Details

Language :
English
ISSN :
2050084X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.31f7cf408b6c4a82a986480e774b45e5
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.78277