Early Crypt Formation Defects in the Uterine Epithelia of Sox17 Heterozygous Mice

Early Crypt Formation Defects in the Uterine Epithelia of Sox17 Heterozygous Mice
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Sox17 杂合子小鼠子宫上皮的早期隐窝形成缺陷

DOI:
10.1159/000513386
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发表时间:
2021
期刊:
影响因子:
2.3
通讯作者:
Kanai-Azuma Masami
Kanai-Azuma Masami
中科院分区:
医学4区
文献类型:
--
作者:
Hirate Yoshikazu;Hayakawa Kana;Nakano Yuki;Kumazawa Shiori;Miura Kento;Kanai Yoshiakira;Kanai-Azuma Masami

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子宫上皮中的SOX 17活性对于小鼠胚胎的植入是必不可少的。以前,我们证明了雌性Sox 17杂合突变小鼠生育力低下,并且需要2个活性拷贝的Sox 17才能正确植入小鼠胚胎。为了了解哪个植入步骤对Sox 17基因剂量最敏感,我们全面研究了Sox 17杂合突变小鼠的表型和RNA转录组。子宫Sox 17的表达急剧变化,根据动情周期和妊娠早期。Sox 17在胚泡着床的接受期表达最高。Sox 17杂合子子宫上皮细胞显示出SOX 9的异位高水平表达,SOX 9是另一种通常在子宫腺中表达的SOX因子。妊娠第5天子宫的三维分析显示,在Sox 17杂合子宫上皮中的健康囊胚附近没有隐窝形成,这表明胚胎归巢的早期缺陷已经发生。全局转录分析显示,双调蛋白(Areg)(一种编码肝素结合表皮生长因子受体配体的基因)的表达在Sox 17 +/−子宫上皮细胞中急剧下降。这些数据意味着,通过在植入部位适当调节SOX 9和AREG表达,需要完整的Sox 17活性来促进早期隐窝形成。
SOX17 activity in the uterine epithelium is essential for the implantation of mouse embryos. Previously, we demonstrated that female Sox17 heterozygous mutant mice are subfertile, and 2 active copies of Sox17 are required for the proper implantation of mouse embryos. To understand which implantation step is most sensitive to the Sox17 gene dosage, we comprehensively investigated the phenotypes and RNA transcriptomes of Sox17 heterozygous mutant mice. Uterine Sox17 expression drastically changed according to estrous cycle and during early pregnancy. The highest Sox17 expression was observed during the receptive period for blastocyst implantation. Sox17 heterozygous uterine epithelia showed ectopic high-level expression of SOX9, another SOX factor that is normally expressed in the uterine gland. Three-dimensional analysis of the uterus on day 5 of pregnancy revealed no crypt formation near the healthy blastocysts in the Sox17 heterozygous uterine epithelium, suggesting that early defects in embryo homing had occurred. Global transcriptional analysis revealed that the expression of Amphiregulin (Areg), a gene encoding a heparin-binding epidermal growth factor receptor ligand, was decreased drastically in Sox17+/− uterine epithelia. These data imply that full Sox17 activity is required to promote early crypt formation through proper regulation of SOX9 and AREG expression at the implantation site.
DOI: 10.1073/pnas.98.3.1047
发表时间: 2001-01-30
影响因子: 11.1
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血浆黄体酮、FSH 和 LH 水平与小鼠植入相关。
DOI: 10.1071/bi9770289
发表时间: 1977
期刊: Australian journal of biological sciences
影响因子: --
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通讯作者: A. GIDLEY‐BAIRD