Yuan Caixia, Li Xianlian, Song Haixia, Fan Lingling, Su Shili, Dong Baihua
Department of Gynecology and Obstetrics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Reproductive Medicine, Shanxi Provincial People's Hospital, Taiyuan, Shanxi 030012, P.R. China.
Exp Ther Med. 2019 Apr;17(4):2547-2556. doi: 10.3892/etm.2019.7265. Epub 2019 Feb 13.
Bone morphogenetic protein (BMP) expression has been observed in the uterus in previous studies. However, the influence of BMP7 on blastocyst implantation remains unclear. Blastocysts first act on luminal endometrial epithelial cells during implantation. The purpose of the present study was to explore the influence of BMP7 on endometrial epithelial cells. A pregnancy animal model, and mouse and human endometrial epithelial cells were used in the present study. Transient knockdown, immunofluorescence assay, embryo implantation, BMP7 silencing, reverse transcription-quantitative polymerase chain reaction, western blotting, immunoprecipitation and Rac1 function assay were also performed. It was revealed that BMP7 concentration was increased in endometrial epithelial cells during the final pre-receptive and receptive stages of receptivity in the mouse endometrium. Additionally, BM7 acted on the transforming growth factor-β receptor, endoglin. Endoglin expression was detected in both stromal and endothelial cells apart from trophoblast expression. Following knockdown of BMP7, Rac-GTP was decreased in endometrial epithelial cells and the uterus. Knockdown of endoglin by small interfering RNA decreased the number of blastocysts and implantation regions. Additionally, BMP7 silencing and endoglin suppression of Ishikawa cells led to impaired JAr spheroid attachment. These findings suggest that BMP7 is associated with receptivity of the endometrium, indicating that BMP7 regulates receptivity of endometrial epithelial cells for implantation of blastocysts via the endoglin pathway.
以往研究已观察到子宫中有骨形态发生蛋白（BMP）表达。然而，BMP7对囊胚着床的影响仍不清楚。囊胚在着床过程中首先作用于子宫内膜腔上皮细胞。本研究的目的是探讨BMP7对子宫内膜上皮细胞的影响。本研究使用了妊娠动物模型以及小鼠和人子宫内膜上皮细胞。还进行了瞬时敲低、免疫荧光分析、胚胎着床、BMP7沉默、逆转录定量聚合酶链反应、蛋白质印迹、免疫沉淀和Rac1功能分析。结果显示，在小鼠子宫内膜接受性的最终非接受期和接受期，子宫内膜上皮细胞中的BMP7浓度升高。此外，BM7作用于转化生长因子-β受体内皮糖蛋白。除滋养层表达外，在内皮细胞和基质细胞中均检测到内皮糖蛋白表达。敲低BMP7后，子宫内膜上皮细胞和子宫中的Rac-GTP减少。用小干扰RNA敲低内皮糖蛋白可减少囊胚数量和着床区域。此外，对Ishikawa细胞进行BMP7沉默和内皮糖蛋白抑制会导致JAr球体附着受损。这些发现表明，BMP7与子宫内膜的接受性相关，提示BMP7通过内皮糖蛋白途径调节子宫内膜上皮细胞对囊胚着床的接受性。
