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 mo...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 Igflr 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.展开更多
基金supported by the National Key R&D Program of China(2017YFC1001402 to H.W.2018YFC1004401 to S.K.)+1 种基金the National Natural Science Foundation of China(81830045 and 82030040 to H.W.,81971388 to S.K.)Institution of Higher Education Projects of Building First-class Discipline Construction in Ningxia Region(NXYLXK2017B05 to G.X.).
文摘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 Igflr 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.
