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关联性标记的SMAD1和SMAD5小鼠线揭示了怀孕早期的转录重编程机制

Zian Liao^1,2,3,4, Suni Tang^1,4, Kaori Nozawa^1,4

¹Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, 77030, USA.

bioRxiv : the preprint server for biology

|December 18, 2023

概括

成功怀孕需要子宫内膜分泌,这涉及孕激素受体 (PR) 和BMP-SMAD1/SMAD5信号. 这项研究揭示了SMAD1/5/5的存在.

科学领域:

生殖生物学生殖生物学
分子内分泌学分子内分泌学
遗传学是一个遗传学.

背景情况:

子宫内膜分泌对于怀孕成功至关重要,由孕激素受体 (PR) 和骨形态蛋白质 (BMP) 信号通路驱动.
在子宫内膜受容性中,BMP-SMAD1/SMAD5和PR信号之间的精确相互作用仍然不完全理解.
了解这些途径对于解决植入失败和改善妊娠结果至关重要.

研究的目的:

调查SMAD1和SMAD5如何在怀孕早期在子宫中整合BMP信号.
确定SMAD1和SMAD5在子宫受体性中的独特和共享的作用.
描述BMP信号在子宫内膜决定中的功能和转化方面.

主要方法:

为SMAD1和SMAD5.5生成新型转基因小鼠系.
在小鼠子宫中对SMAD1,SMAD5和PR分布的全基因组分析.
在人类子宫内膜层细胞中进行SMAD1/5敲除,以评估基因表达.

主要成果:

在植入窗口期间确定了SMAD1和SMAD5的独特和共享的基因组结合点.
在孕妇子宫中发现了一个保存的SMAD1,SMAD5和PR基因组结合签名.
证明SMAD1/5敲击抑制了人类细胞中关键的叶和PR反应基因.

结论:

在怀孕初期,SMAD1和SMAD5是BMP信号传递和孕激素的转录反应的基本调解者.
开发了新的转基因工具,用于研究生殖环境中的BMP信号.
这些发现阐明了底层子宫内膜受体性和成功植入的关键分子机制.

关键词:

它们是SMAD蛋白质.骨形态遗传蛋白质骨形态遗传蛋白质个人化的决定性.这是子宫内膜的内分泌物.孕激素是孕激素的一种.这是子宫,子宫.

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