BMP7 coordinates endometrial epithelial cell receptivity for blastocyst implantation through the endoglin pathway in cell lines and a mouse model

Abstract

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, in vitro 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.

Assessment of BMP7, SMAD4, and CDH1 Expression Profile and Regulatory miRNA-542-3p in Eutopic and Ectopic Endometrium of Women with Endometriosis

“…In our work, we focused on assessing the expression of BMP7 mRNA in the eutopic endometrium of women with endometriosis, confirming its significant upregulation compared to the control group. Other authors also showed increased expression of BMP7 , but before implantation, during the receptive period, compared with its baseline concentration in endometrial epithelial cells in mice [ 84 ]. Additionally, in the human endometrium, the expression of this gene was observed in cultured endometrial stromal cells with a high degree of decidualization [ 82 ].…”

Maternal exposure to an enriched environment promotes uterine vascular remodeling and prevents embryo loss in mice

“…Within the wide range of mediators involved in the vascular process of early pregnancy, different authors have shown the importance of endoglin, von Willebrand factor and VEGF. Endoglin is expressed in the apical face of the luminal epithelium of the endometrium and the primary and secondary decidua in mice (Chadchan et al 2016, Yuan et al 2019. It has been shown that endoglin participates in the adhesion of the blastocyst to the uterus and modulates uterine receptivity during the window of implantation.…”

“…In the present work, we observed an increase in endoglin expression at the implantation sites of females exposed to the EE. This increase might be related to the reception of signals released by the embryo (Chadchan et al 2016, Yuan et al 2019, which stimulate vascular remodeling of the maternal-fetal interface. On the other hand, the EE action on vascular remodeling seems not to be mediated by VEGFA or von Willebrand factor as we did not observe any differences between control and EE mice.…”

State-of-the-art of the Bone Morphogenetic Protein research field: 13th International BMP Conference, Dubrovnik 2022

“…BMPs are shown to directly control endometrial receptivity via activin receptor type 2 A (ACVR2A) and SMAD1/5 signaling pathway (106,107). BMP7 is also involved in receptivity of the endometrium, regulating blastocyst implantation via the endoglin pathway (108). Upon implantation, BMP2 was shown to promote trophoblast cell invasion (109).…”