scholarly journals A Gelatin Hydrogel to Study Endometrial Angiogenesis and Trophoblast Invasion

2019 ◽  
Author(s):  
Samantha G. Zambuto ◽  
Kathryn B.H. Clancy ◽  
Brendan A.C. Harley

ABSTRACTAs the lining of the uterus and site of blastocyst implantation, the endometrium is a dynamic tissue that undergoes rapid cycles of growth, breakdown, and remodeling each menstrual cycle. Significant vascular remodeling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodeling enhance blood flow to the embryo ahead of placentation. Insight into endometrial vascular remodeling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective for this study was to develop a tissue engineering platform to investigate processes of endometrial angiogenesis and trophoblast invasion in a 3D environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue. Further, the hydrogel supports the formation of stable endometrial endothelial cell networks and attachment of a stratified endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment, and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.

2019 ◽  
Vol 9 (5) ◽  
pp. 20190016 ◽  
Author(s):  
Samantha G. Zambuto ◽  
Kathryn B. H. Clancy ◽  
Brendan A. C. Harley

The endometrium is the lining of the uterus and site of blastocyst implantation. Each menstrual cycle, the endometrium cycles through rapid phases of growth, remodelling and breakdown. Significant vascular remodelling is also driven by trophoblast cells that form the outer layer of the blastocyst. Trophoblast invasion and remodelling enhance blood flow to the embryo ahead of placentation. Understanding the mechanisms of endometrial vascular remodelling and trophoblast invasion would provide key insights into endometrial physiology and cellular interactions critical for establishment of pregnancy. The objective of this study was to develop a tissue engineering platform to investigate the processes of endometrial angiogenesis and trophoblast invasion in a three-dimensional environment. We report adaptation of a methacrylamide-functionalized gelatin hydrogel that presents matrix stiffness in the range of the native tissue, supports the formation of endometrial endothelial cell networks with human umbilical vein endothelial cells and human endometrial stromal cells as an artificial endometrial perivascular niche and the culture of an endometrial epithelial cell layer, enables culture of a hormone-responsive stromal compartment and provides the capacity to monitor the kinetics of trophoblast invasion. With these studies, we provide a series of techniques that will instruct researchers in the development of endometrial models of increasing complexity.


Reproduction ◽  
2007 ◽  
Vol 134 (5) ◽  
pp. 635-643 ◽  
Author(s):  
Thomas G Kennedy ◽  
Carolina Gillio-Meina ◽  
Sen Han Phang

The process of blastocyst implantation in mammals is remarkably variable, especially in the extent of trophoblast invasion of the endometrium. In most species studied, the earliest macroscopically identifiable sign of blastocyst implantation is an increase in endometrial vascular permeability in areas adjacent to the blastocysts. This is followed in species with invasive implantation by decidualization, again localized to areas adjacent to the blastocysts. In some species, the application of a stimulus to the endometrium can result in increased endometrial vascular permeability and decidualization. Based initially on studies utilizing inhibitors of prostaglandin (PG) synthesis and more recently on studies using the techniques of transgenics, considerable evidence has accumulated indicating that PGs have an important role in the early events of implantation and artificially induced decidualization. However, which PGs are involved remains controversial. There may be differences between species, and different PGs may be involved at different times.


2015 ◽  
Vol 308 (3) ◽  
pp. L229-L252 ◽  
Author(s):  
Steven C. Pugliese ◽  
Jens M. Poth ◽  
Mehdi A. Fini ◽  
Andrea Olschewski ◽  
Karim C. El Kasmi ◽  
...  

Hypoxic pulmonary hypertension (PH) comprises a heterogeneous group of diseases sharing the common feature of chronic hypoxia-induced pulmonary vascular remodeling. The disease is usually characterized by mild to moderate pulmonary vascular remodeling that is largely thought to be reversible compared with the progressive irreversible disease seen in World Health Organization (WHO) group I disease. However, in these patients, the presence of PH significantly worsens morbidity and mortality. In addition, a small subset of patients with hypoxic PH develop “out-of-proportion” severe pulmonary hypertension characterized by pulmonary vascular remodeling that is irreversible and similar to that in WHO group I disease. In all cases of hypoxia-related vascular remodeling and PH, inflammation, particularly persistent inflammation, is thought to play a role. This review focuses on the effects of hypoxia on pulmonary vascular cells and the signaling pathways involved in the initiation and perpetuation of vascular inflammation, especially as they relate to vascular remodeling and transition to chronic irreversible PH. We hypothesize that the combination of hypoxia and local tissue factors/cytokines (“second hit”) antagonizes tissue homeostatic cellular interactions between mesenchymal cells (fibroblasts and/or smooth muscle cells) and macrophages and arrests these cells in an epigenetically locked and permanently activated proremodeling and proinflammatory phenotype. This aberrant cellular cross-talk between mesenchymal cells and macrophages promotes transition to chronic nonresolving inflammation and vascular remodeling, perpetuating PH. A better understanding of these signaling pathways may lead to the development of specific therapeutic targets, as none are currently available for WHO group III disease.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Naguib Salleh

Prostaglandins (PGs), derivatives of arachidonic acid, play an indispensable role in embryo implantation. PGs have been reported to participate in the increase in vascular permeability, stromal decidualization, blastocyst growth and development, leukocyte recruitment, embryo transport, trophoblast invasion, and extracellular matrix remodeling during implantation. Deranged PGs syntheses and actions will result in implantation failure. This review summarizes up-to-date literatures on the role of PGs in blastocyst implantation which could provide a broad perspective to guide further research in this field.


Placenta ◽  
2015 ◽  
Vol 36 (10) ◽  
pp. 1087-1094 ◽  
Author(s):  
Ping Li ◽  
Hui Peng ◽  
Wen-hui Lu ◽  
Han-lin Shuai ◽  
Qing-bin Zha ◽  
...  

2021 ◽  
Vol 5 (2) ◽  
pp. 161-177
Author(s):  
Dona Mirsa Putri ◽  
Ariadi Ariadi ◽  
Yusrawati Yusrawati

Iron deficiency anemia that followed by low serum ferritin levels in early pregnancy has an indirect impact on decreasing the expression of Brain Derived Neurotrophic Factor (BDNF) in the maternal hippocampus. BDNF together with its receptor tyrosine kinase B (TrkB) induced the expression of metalloproteinase-9 (MMP-9) which plays an important role in blastocyst implantation, trophoblast invasion and placental development. Decreasing BDNF levels can interfere with those process which caused imbalance of pro-angiogenic and anti-angiogenic factors such as VEGF, PIGF, sFlt1 and sEng that leads to preeclampsia. This study aims to determine the correlation between ferritin and BDNF serum levels in preeclampsia.Keywords: Preeclampsia, ferritin, iron deficiency anemia, Brain Derived Neurotrophic Factor


2020 ◽  
Author(s):  
Suzanna Queckbörner ◽  
Carolina von Grothusen ◽  
Nageswara Boggavarapu ◽  
Lindsay C. Davies ◽  
Kristina Gemzell-Danielsson

AbstractThe endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial samples were obtained during the proliferative phase of the menstrual cycle from healthy women aged 24–32 years. Within the stromal compartment multiple stromal populations were found, suggestive of specific stromal niches that control inflammation and extracellular matrix composition. Ten different stromal cell and two pericyte subsets were identified. Applying different R packages (Seurat, SingleR, Velocyto) we determined cell cluster diversity and cell lineage/trajectory while using external data to validate our findings. By understanding healthy regeneration in the described stromal compartments, we aim to identify points of intervention for novel therapy development in order to treat benign gynaecological disorders affecting endometrial regeneration and proliferation e.g. endometriosis and Asherman’s syndrome.


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