scholarly journals Activation of Blood Vessel Development in Endometrial Stromal Cells In Vitro Cocultured with Human Peri-Implantation Embryos Revealed by Single-Cell RNA-Seq

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 367
Author(s):  
Bo Lv ◽  
Xiaoyu Xu ◽  
Xunyi Zhang ◽  
Lingbin Qi ◽  
Wen He ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Single Cell ◽  
Stromal Cells ◽  
Differentially Expressed Gene ◽  
Trophoblast Cells ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Blood Vessel Development ◽  
Vessel Development

In humans, the maternal endometrium participates in the physical and physiological interaction with the blastocyst to begin implantation. A bidirectional crosstalk is critical for normal implantation and then a successful pregnancy. While several studies have used animal models or cell lines to study this step, little knowledge was acquired to address the role of endometrial cells in humans. Here, we analyzed single-cell sequencing data from a previous study including 24 non-coculture endometrial stromal cells (EmSCs) and 57 EmSCs after coculture with embryos. We further explored the transcriptomic changes in EmSCs and their interactions with trophoblast cells after coculture. Differentially expressed gene (DEG) analysis showed 1783 upregulated genes and 569 downregulated genes in the cocultured embryos. Weight gene coexpression network and gene ontology analysis of these DEGs showed a higher expression of RAMP1, LTBP1, and LRP1 in EmSCs after coculture, indicating the enrichment of biological processes in blood vessel development and female pregnancy. These data imply that EmSCs start blood vessel development at the implantation stage. Compared with endometrium data in vivo at the implantation window, key pathways including epithelial cell development and oxygen response were involved at this stage. Further analysis using CellphoneDB shed light on the interactions between EmSCs and embryonic trophoblasts, suggesting the important role of integrins and fibroblast growth factor pathways during implantation. Taken together, our work reveals the synchronization signaling and pathways happening at the implantation stage involving the acquisition of receptivity in EmSCs and the interaction between EmSCs and trophoblast cells.

scholarly journals Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

2021 ◽  
Author(s):  
Dariusz Szukiewicz ◽  
Aleksandra Stangret ◽  
Carmen Ruiz-Ruiz ◽  
Enrique G. Olivares ◽  
Olga Soriţău ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Uterine Cavity ◽  
Retrograde Transport ◽  
Surrounding Tissue ◽  
Pelvic Cavity ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Estrogen Exposure ◽  
Chronic Inflammatory Condition

AbstractEndometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis.

Role of tissue factor in embryonic blood vessel development

Nature ◽  
1996 ◽  
Vol 383 (6595) ◽  
pp. 73-75 ◽  
Author(s):  
Peter Carmeliet ◽  
Nigel Mackman ◽  
Lieve Moons ◽  
Thomas Luther ◽  
Pierre Gressens ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Tissue Factor ◽  
Blood Vessel Development ◽  
Vessel Development

LIM Kinase 1 Mediates Estradiol Effects on the Phosphorylation of Cofilin1 in Eutopic Endometrial Stromal Cells During the Invasion and Proliferation of Endometriosis

2019 ◽  
Vol 26 (11) ◽  
pp. 1499-1505 ◽  
Author(s):  
Jing Liu ◽  
Zhifang Zhang ◽  
Jiamei Liu ◽  
Danbo Wang
Keyword(s):  
Rna Interference ◽  
Cell Invasion ◽  
Stromal Cells ◽  
Endometrial Stromal Cells ◽  
Lim Kinase ◽  
Endometrial Cells ◽  
Lim Kinase 1 ◽  
Gynecological Disease ◽  
Cell Invasiveness

Endometriosis is an estrogen-dependent gynecological disease; however, the mechanism by which estradiol promotes the development of endometriosis, including invasion and proliferation, remains unclear. Estradiol is involved in cell invasion and proliferation by regulating the cytoskeleton. The abnormally high expression of cytoskeletal regulators (LIM kinase 1 [LIMK1] and cofilin1) is closely related to increased invasiveness and proliferation of eutopic endometrial stromal cells from endometriosis patients compared to normal eutopic endometrial cells. The aim of this study was to analyze the role of estradiol during invasion and proliferation through the LIMK1/cofilin1 pathway in the endometrium of women with endometriosis. To address this, primary eutopic endometrial stromal cells were isolated from the uteri of patients with endometriosis and cultured without estradiol. The phosphorylation of cofilin1 was analyzed by western blotting. Cell invasiveness and proliferation were evaluated following LIMK1 knockdown by RNA interference technology. We found that, before LIMK1silencing, the phosphorylation levels of cofilin1 and LIMK1 of eutopic endometrial stromal cells from endometriosis patients treated with estradiol were higher than cells not treated with estradiol ( P < .05 and P < .01, respectively). The total levels of cofilin1 and LIMK1 protein did not change ( P > .05 and P > .05, respectively). After LIMK1 silencing, the phosphorylation of cofilin1 by estradiol was significantly reduced, and invasiveness and proliferation were clearly and concurrently decreased ( P < .05 and P < .05, respectively). Thus, the phosphorylation of cofilin1 by estradiol is mediated by LIMK1, and estradiol is involved in regulating cell invasion and proliferation in endometriotic patients through the LIMK1/cofilin1 pathway.

scholarly journals 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol ameliorates the progression of endometriosis by regulating GSTM4 expression to inhibit proliferation and induce apoptosis

2021 ◽  
Author(s):  
Wei Liu ◽  
Na Zhang ◽  
Yanbo Du ◽  
Xiaoqiang Liu ◽  
Jinlong Ma ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Benign Disease ◽  
Glutathione S Transferase ◽  
Endometrial Stromal Cells ◽  
Endometrial Cells ◽  
Oxidative Balance ◽  
Induced Apoptosis

Abstract Background: Endometriosis is a chronic disease associated with disorder of the oxidative balance and chronic inflammation. Although endometriosis is a benign disease, it has the characteristics properties similar to malignant cancer.Methods: The present study aim to investigate the role of glutathione S-transferase Mu class 4 (GSTM4), and tested if 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) could regulate GSTM4 expression to affect cell proliferation, migration, invasion and apoptosis in endometriosis. Expression of GSTM4 was detected by immunohistochemistry in 15 cases of endometriosis patients and compared with 15 healthy controls. Primary endometrial cells were analyzed by western blotting (WB) to determine expression of GSTM4, PCNA, MMP-9, Survivin, Bcl-xl, Bax, Keap1 and Nrf2. CCK8 and transwell assays were used to study the effects of GSTM4 and NBEHEX on endometrial cells. The effect on apoptosis was analysised by flow cytometry. Results: The expression of GSTM4 was significantly increased in endometriosis than those from controls (p<0.01). The results suggested that NBDHEX negatively regulates GSTM4 expression, induces cell proliferation, migration, invasion, and promotes cell apoptosis. NBDHEX decreased the expression of GSTM4 (p<0.05), PCNA (p<0.05), MMP-9 (p<0.01), Survivin (p<0.05) and Bcl-xl (p<0.05) , along with increased expression of Bax (p<0.05). The results also showed that NBDHEX decreased the expression of Nrf2 (p<0.05), but had no effect on the expression of Keap1(p>0.05). After transfection with si-GSTM4, the protein level was down-regulated by nearly 70% (p<0.05). Silencing of GSTM4 depressed the proliferation, migration, invasion and gene expression of endometrial stromal cells in patients with endometriosis and controls. Knockdown of GSTM4 interacting with Nrf2 induced apoptosis by decreasing the expression of Survivin (p<0.05), Bcl-xl (p<0.05) and increasing the expression of Bax (p<0.05) , but it did not affect the expression of Keap1(p>0.05) in endometriosis and controls. Conclusions: Inhibition of GSTM4 by NBDHEX suppresses the cell viability growth, migration, invasion and interact with Nrf2 to induce apoptosis, but has no effect on the expression of Keap1 in endometriosis. The use of siRNA to knockdown GSTM4 more accurately confirmed its ability to ameliorate the progression of endometriosis. NBDHEX may have therapeutic potential in the treatment of endometriosis.

scholarly journals The role of blood flow and microRNAs in blood vessel development

2011 ◽  
Vol 55 (4-5) ◽  
pp. 419-429 ◽  
Author(s):  
Dong Liu ◽  
Janna Krueger ◽  
Ferdinand Le Noble
Keyword(s):  
Blood Flow ◽  
Blood Vessel ◽  
Blood Vessel Development ◽  
Vessel Development
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