研究动态
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胚胎期β-连环蛋白是子宫为着床做准备所必须的。

Embryonic β-Catenin Is Required for Priming of the Uterus to Implantation.

发表日期:2023 Mar
作者: Youki Takezawa, Maki Iwai, Yukiko Fujiki, Ryo Yokomizo, Harue Kishigami, Mami Miyado, Natsuko Kawano, Mitsutoshi Yamada, Miyuki Shindo, Miki Suzuki, Ban Sato, Daiki Katano, Shintaro Kamijo, Toshio Hamatani, Mamoru Tanaka, Akihiro Umezawa, Woojin Kang, Kenji Miyado
来源: Protein & Cell

摘要:

重复植入失败是健康女性不孕的主要原因之一。子宫内β-连接素(CTNNB1)在植入过程中发挥关键作用。然而,胚胎CTNNB1在植入过程中的作用尚不清楚。我们通过分析携带Ctnnb1缺陷(Ctnnb1Δ/Δ)胚胎的小鼠来探讨这个问题。Ctnnb1Δ/Δ胚胎是由携带Ctnnb1缺陷的卵子和精子交配产生的。我们发现,Ctnnb1Δ/Δ胚胎发育到囊胚阶段后,被吸收了,留下了空的蜕膜囊。此外,对植入至关重要的子宫因子白血病抑制因子在Ctnnb1Δ/Δ囊胚中无法检测到。此外,决定滋养层细胞命运的转录因子CDX2在Ctnnb1Δ/Δ囊胚中没有观察到。宫内注射子宫液(来自对照小鼠)和重组鼠白血病抑制因子蛋白质使子宫对Ctnnb1Δ/Δ囊胚产生了反应。这些结果表明,胚胎CTNNB1是分泌囊胚源性因子以打开植入窗口所必需的,而通过使用补充材料,可以诱导子宫对植入的反应。因此,我们的结果可能有助于发现类似的机制在人类中,从而更好地理解重复植入失败的病因。版权所有©2022年美国和加拿大病理学院。由Elsevier公司出版。保留所有权利。
Repeated implantation failure is a major cause of infertility among healthy women. Uterine β-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1Δ/Δ) embryos. Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.Copyright © 2022 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.