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<p>Uterine receptivity is essential for successful implantation. In mice, uterine receptivity begins with the secretion of LIF from uterine glands stimulated by estrogen on the morning of day 4 pregnancy. We hypothesize that gland readiness for estrogen stimulation is indispensable for uterine receptivity. The current study reveals that uterine glands undergo a differentiation process with expanded branching during the preimplantation period. The single-cell RNA profiling of glandular cells identifies that LIF is expressed exclusively in a <i>Prss29</i>+ subgroup of glandular cells on day 4 of pregnancy. Interestingly, <i>Foxa2</i>-deficient glands lacking LIF production fail to develop branches and the functional <i>Prss29</i>+ subgroup. This <i>Prss29</i>+ subgroup develops prior to estrogen secretion. Collectively, our findings show that uterine glands undergo a FOXA2-dependent maturation process to acquire the competence, named “transitional phase”, for entering the receptive phase. The “transitional phase”, predicting uterine receptivity one day before implantation, is a landmark concept in uterine receptivity.</p>

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Foxa2-dependent uterine glandular cell differentiation is essential for successful implantation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月12日

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  • Zhaoyu Jia,
  • Bo Li,
  • Mitsunori Matsuo,
  • Amanda Dewar,
  • Anxhela Mustafaraj,
  • Sudhansu K. Dey,
  • Jia Yuan,
  • Xiaofei Sun

摘要

Uterine receptivity is essential for successful implantation. In mice, uterine receptivity begins with the secretion of LIF from uterine glands stimulated by estrogen on the morning of day 4 pregnancy. We hypothesize that gland readiness for estrogen stimulation is indispensable for uterine receptivity. The current study reveals that uterine glands undergo a differentiation process with expanded branching during the preimplantation period. The single-cell RNA profiling of glandular cells identifies that LIF is expressed exclusively in a Prss29+ subgroup of glandular cells on day 4 of pregnancy. Interestingly, Foxa2-deficient glands lacking LIF production fail to develop branches and the functional Prss29+ subgroup. This Prss29+ subgroup develops prior to estrogen secretion. Collectively, our findings show that uterine glands undergo a FOXA2-dependent maturation process to acquire the competence, named “transitional phase”, for entering the receptive phase. The “transitional phase”, predicting uterine receptivity one day before implantation, is a landmark concept in uterine receptivity.