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Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice

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...

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Autores principales: Matsuo, Mitsunori, Yuan, Jia, Kim, Yeon Sun, Dewar, Amanda, Fujita, Hidetoshi, Dey, Sudhansu K, Sun, Xiaofei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355561/
https://www.ncbi.nlm.nih.gov/pubmed/35861728
http://dx.doi.org/10.7554/eLife.78277
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author Matsuo, Mitsunori
Yuan, Jia
Kim, Yeon Sun
Dewar, Amanda
Fujita, Hidetoshi
Dey, Sudhansu K
Sun, Xiaofei
author_facet Matsuo, Mitsunori
Yuan, Jia
Kim, Yeon Sun
Dewar, Amanda
Fujita, Hidetoshi
Dey, Sudhansu K
Sun, Xiaofei
author_sort Matsuo, Mitsunori
collection PubMed
description 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.
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spelling pubmed-93555612022-08-06 Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice Matsuo, Mitsunori Yuan, Jia Kim, Yeon Sun Dewar, Amanda Fujita, Hidetoshi Dey, Sudhansu K Sun, Xiaofei eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2022-07-21 /pmc/articles/PMC9355561/ /pubmed/35861728 http://dx.doi.org/10.7554/eLife.78277 Text en © 2022, Matsuo, Yuan, Kim et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology
Matsuo, Mitsunori
Yuan, Jia
Kim, Yeon Sun
Dewar, Amanda
Fujita, Hidetoshi
Dey, Sudhansu K
Sun, Xiaofei
Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title_full Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title_fullStr Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title_full_unstemmed Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title_short Targeted depletion of uterine glandular Foxa2 induces embryonic diapause in mice
title_sort targeted depletion of uterine glandular foxa2 induces embryonic diapause in mice
topic Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355561/
https://www.ncbi.nlm.nih.gov/pubmed/35861728
http://dx.doi.org/10.7554/eLife.78277
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