Murine uterine gland branching is necessary for gland function in implantation.
Murine uterine gland branching is necessary for gland function in implantation.
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小鼠子宫腺分支对于着床时的腺体功能是必需的。
DOI：
10.1101/2023.11.01.565233
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Arora,Ripla
中科院分区：
文献类型：
--
作者：
Granger,Katrina;Fitch,Sarah;Shen,May;Lloyd,Jarrett;Bhurke,Aishwarya;Hancock,Jonathan;Ye,Xiaoqin;Arora,Ripla
子宫腺体是分支管状结构，其分泌物对于妊娠成功至关重要。众所周知，白血病抑制因子（LIF）的植入前腺体表达对于胚胎植入至关重要。然而，子宫腺体结构对腺体分泌物（例如 LIF）的贡献尚不清楚。在这里，我们使用雌激素受体 1 (ESR1) 信号缺陷的小鼠来揭示 ESR1 信号在腺体分支中的作用以及分支结构在 LIF 分泌和胚胎植入中的作用。我们观察到，使用孕酮受体PgrC删除新生儿子宫上皮、间质和肌肉中的ESR1会导致腺芽阶段子宫腺体发育受阻。使用苗勒氏管 Cre 系 Pax2Cre 进行 ESR1 的胚胎上皮缺失，显示腺芽伸长，但腺体分支失败。使用乳铁蛋白-Cre (LtfCre) 减少成人子宫上皮中的 ESR1，显示出正常分支的子宫腺体。 Pax2CreEsr1flox/floxuteri 的无分支腺体无法表达植入前腺体 Lif，从而阻止着床室形成和胚胎沿子宫系膜-抗时膜轴排列。相比之下，来自LtfCreEsr1flox/floxuteri的分支腺体显示ESR1和腺体Lifre的表达减少，导致着床室形成和胚胎-子宫轴排列延迟，但小鼠产下的幼崽数量正常。最后，即使在存在雌激素的情况下，对照小鼠的青春期前无分支腺体在管腔上皮中表达Lifin，但在腺上皮中不表达Lifin。这些数据强烈表明，分支腺体对于植入前腺体Lif表达对于植入成功是必要的。我们的研究首次确定了子宫腺体的分支结构和分泌功能之间的关系，并为理解子宫腺体结构-功能如何有助于妊娠成功提供了一个框架。
Uterine glands are branched, tubular structures whose secretions are essential for pregnancy success. It is known that pre-implantation glandular expression of leukemia inhibitory factor (LIF) is crucial for embryo implantation; however, the contribution of uterine gland structure to gland secretions, such as LIF, is not known. Here, we use mice deficient in estrogen receptor 1 (ESR1) signaling to uncover the role of ESR1 signaling in gland branching and the role of a branched structure in LIF secretion and embryo implantation. We observed that deletion of ESR1 in neonatal uterine epithelium, stroma, and muscle using the progesterone receptorPgrCrecauses a block in uterine gland development at the gland bud stage. Embryonic epithelial deletion of ESR1 using a Müllerian duct Cre line,Pax2Cre, displays gland bud elongation but a failure in gland branching. Reduction of ESR1 in adult uterine epithelium using the lactoferrin-Cre (LtfCre) displays normally branched uterine glands. Unbranched glands fromPax2CreEsr1flox/floxuteri fail to express glandular pre-implantationLif, preventing implantation chamber formation and embryo alignment along the uterine mesometrial–antimesometrial axis. In contrast, branched glands fromLtfCreEsr1flox/floxuteri display reduced expression of ESR1 and glandularLifresulting in delayed implantation chamber formation and embryo–uterine axes alignment but mice deliver a normal number of pups. Finally, pre-pubertal unbranched glands in control mice expressLifin the luminal epithelium but fail to expressLifin the glandular epithelium, even in the presence of estrogen. These data strongly suggest that branched glands are necessary for pre-implantation glandularLifexpression for implantation success. Our study is the first to identify a relationship between the branched structure and secretory function of uterine glands and provides a framework for understanding how uterine gland structure–function contributes to pregnancy success.
虎鲸中耳（Orcinus orca）的解剖结构
影响因子：
2.8
作者：
S. Nummela;T. Reuter;S. Hemilä;P. Holmberg;P. Paukku
通讯作者：
P. Paukku