Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation.
Sequential activation of uterine epithelial IGF1R by stromal IGF1 and embryonic IGF2 directs normal uterine preparation for embryo implantation.
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间质IGF1和胚胎IGF2顺序激活子宫上皮IGF1 R，指导胚胎着床的正常子宫准备。
DOI：
10.1093/jmcb/mjab034
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发表时间：
2021-12-06
影响因子：
5.5
通讯作者：
Kong S
中科院分区：
文献类型：
--
作者：
Zhou C;Lv M;Wang P;Guo C;Ni Z;Bao H;Tang Y;Cai H;Lu J;Deng W;Yang X;Xia G;Wang H;Wang C;Kong S
在人类和啮齿动物中，胚胎植入都是通过将胚泡附着到子宫上皮来启动的。对于胚泡附着，子宫上皮首先需要在结构和分子水平上进行转化，然后才能启动与滋养外胚层的相互作用。这一过程中的任何干扰都将导致植入失败或长期不良妊娠结局。内分泌类固醇激素通过核受体发挥作用，与子宫或胚胎产生的局部分子结合，促进着床。胰岛素样生长因子(IGF)信号在妊娠过程中起着至关重要的作用。然而，它在植入过程中的生理功能仍然难以捉摸。本研究发现，子宫内有条件缺失Igf1r基因的小鼠出现了不孕症，其主要原因是子宫容受性障碍和胚胎着床异常。从机制上讲，我们发现，在妊娠D4对强食性雌激素的反应中，上皮IGF1R在基质细胞产生IGF1的刺激下，促进了上皮STAT3的激活，以调节上皮的去极化。此外，胚胎来源的IGF2可以通过IGF1R激活上皮细胞ERK1/2和STAT3信号，这对COX2的转录和正常的附着反应是至关重要的。总之，我们的研究结果表明，在着床过程中，子宫间质IGF1和胚胎IGF2依次激活上皮性IGF1R，以保证正常的上皮性分化。
Embryo implantation in both humans and rodents is initiated by the attachment of a blastocyst to the uterine epithelium. For blastocyst attachment, the uterine epithelium needs to transform at both the structural and molecular levels first, and then initiate the interaction with trophectoderm. Any perturbation during this process will result in implantation failure or long-term adverse pregnancy outcomes. Endocrine steroid hormones, which function through nuclear receptors, combine with the local molecules produced by the uteri or embryo to facilitate implantation. The insulin-like growth factor (IGF) signaling has been reported to play a vital role during pregnancy. However, its physiological function during implantation remains elusive. This study revealed that mice with conditional deletion of Igf1r gene in uteri suffered from subfertility, mainly due to the disturbed uterine receptivity and abnormal embryo implantation. Mechanistically, we uncovered that in response to the nidatory estrogen on D4 of pregnancy, the epithelial IGF1R, stimulated by the stromal cell-produced IGF1, facilitated epithelial STAT3 activation to modulate the epithelial depolarity. Furthermore, embryonic derived IGF2 could activate both the epithelial ERK1/2 and STAT3 signaling through IGF1R, which was critical for the transcription of Cox2 and normal attachment reaction. In brief, our data revealed that epithelial IGF1R was sequentially activated by the uterine stromal IGF1 and embryonic IGF2 to guarantee normal epithelium differentiation during the implantation process.
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DOI：
10.1073/pnas.0402597101
发表时间：
2004-07-13
影响因子：
11.1
作者：
Hamatani, T;Daikoku, T;Dey, SK
通讯作者：
Dey, SK
影响因子：
8
作者：
Li, Ang;Chen, Ping;Kang, Jiuhong
通讯作者：
Kang, Jiuhong
DOI：
10.1073/pnas.98.3.1047
发表时间：
2001-01-30
影响因子：
11.1
作者：
Paria, BC;Ma, WG;Hogan, BLM
通讯作者：
Hogan, BLM
影响因子：
5.8
作者：
Cha J;Sun X;Bartos A;Fenelon J;Lefèvre P;Daikoku T;Shaw G;Maxson R;Murphy BD;Renfree MB;Dey SK
通讯作者：
Dey SK
影响因子：
4.8
作者：
Daikoku, Takiko;Ogawa, Yuya;Dey, Sudhansu K.
通讯作者：
Dey, Sudhansu K.