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发情周期中 Notch 信号在小鼠输卵管和子宫中的动态变化。

Dynamics of Notch signalling in the mouse oviduct and uterus during the oestrous cycle.

作者信息

Murta D, Batista M, Trindade A, Silva E, Mateus L, Duarte A, Lopes-da-Costa L

出版信息

Reprod Fertil Dev. 2015 May 5. doi: 10.1071/RD15029.

Abstract

The oviduct and uterus undergo extensive cellular remodelling during the oestrous cycle, requiring finely tuned intercellular communication. Notch is an evolutionarily conserved cell signalling pathway implicated in cell fate decisions in several tissues. In the present study we evaluated the quantitative real-time polymerase chain reaction (real-time qPCR) and expression (immunohistochemistry) patterns of Notch components (Notch1-4, Delta-like 1 (Dll1), Delta-like 4 (Dll4), Jagged1-2) and effector (hairy/enhancer of split (Hes) 1-2, Hes5 and Notch-Regulated Ankyrin Repeat-Containing Protein (Nrarp)) genes in the mouse oviduct and uterus throughout the oestrous cycle. Notch genes are differentially transcribed and expressed in the mouse oviduct and uterus throughout the oestrous cycle. The correlated transcription levels of Notch components and effector genes, and the nuclear detection of Notch effector proteins, indicate that Notch signalling is active. The correlation between transcription levels of Notch genes and progesterone concentrations, and the association between expression of Notch proteins and progesterone receptor (PR) activation, indicate direct progesterone regulation of Notch signalling. The expression patterns of Notch proteins are spatially and temporally specific, resulting in unique expression combinations of Notch receptor, ligand and effector genes in the oviduct luminal epithelium, uterus luminal and glandular epithelia and uterine stroma throughout the oestrous cycle. Together, the results of the present study imply a regulatory role for Notch signalling in oviduct and uterine cellular remodelling occurring throughout the oestrous cycle.

摘要

在发情周期中,输卵管和子宫会经历广泛的细胞重塑,这需要精确调控的细胞间通讯。Notch是一种在进化上保守的细胞信号通路,参与多种组织中的细胞命运决定。在本研究中,我们评估了小鼠输卵管和子宫在整个发情周期中Notch成分(Notch1 - 4、Delta样1(Dll1)、Delta样4(Dll4)、Jagged1 - 2)和效应器(毛状/分裂增强子(Hes)1 - 2、Hes5和Notch调节的含锚蛋白重复序列蛋白(Nrarp))基因的定量实时聚合酶链反应(实时定量PCR)和表达(免疫组织化学)模式。Notch基因在小鼠输卵管和子宫的整个发情周期中差异转录和表达。Notch成分与效应器基因的相关转录水平以及Notch效应蛋白的核检测表明Notch信号是活跃的。Notch基因转录水平与孕酮浓度之间的相关性,以及Notch蛋白表达与孕酮受体(PR)激活之间的关联,表明孕酮直接调节Notch信号。Notch蛋白的表达模式在空间和时间上具有特异性,导致在发情周期中输卵管腔上皮、子宫腔和腺上皮以及子宫基质中Notch受体、配体和效应器基因出现独特的表达组合。本研究结果共同表明Notch信号在整个发情周期中输卵管和子宫细胞重塑中起调节作用。

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