Download Statistics
Download StatisticsAlshalal, Israa Abdullah Rashid (2020). Development of in vitro models to investigate the role of decidualisation, PDGF, and ho-1 on stromal – trophoblast interaction. University of Birmingham. Ph.D.
|
Israa2020PhD.pdf
Text Available under License All rights reserved. Download (7MB) | Preview |
Abstract
Decidualisation of human endometrial stromal cells (hESC) is essential for embryo implantation. As ethical barriers prevent investigation of human implantation in vivo, this project aimed to develop convenient/reliable co-culture models to evaluate the activity of platelet-derived growth factors (PDGF) and the anti-inflammatory/anti-oxidant haem-oxygenase-1 (HO-1) in hESC–trophoblast interactions. The St-T1b cell line and primary hESC were decidualised in vitro and HTR-8 trophoblast line grown as spheroids and used to develop trophoblast-spheroid expansion and invasion/sprouting assays. Fluorescence cell-labelling coupled with ImageJ/trainable weka plugin facilitated monitoring/analysis of assays over 72 h. Decidualisation of hESC reduced their migration in scratch-wound assays, inhibited trophoblast sprouting and promoted trophoblast-spheroid spreading. PDGF-AA was down-regulated whilst PDGF-α/-β receptor expression increased with hESC decidualisation. PDGF-BB increased hESC migration and HTR-8 trophoblast spheroid expansion and invasion in the presence of decidual hESC. HO-1 was upregulated during hESC decidualisation in a forkhead box-O1-dependent manner. Induction of HO-1 inhibited hESC migration and increased HTR-8-spheroid invasion. VEGF secretion increased, whereas sFlt-1 levels reduced with hESC decidualisation. Surprisingly, HO-1 induction enhanced sFlt-1 and VEGF expression in hESC and HTR-8 cells. Collectively, the results support use of these in vitro models as a platform to evaluate hESC decidualisation and other factors on trophoblast expansion/invasion and identify decidual regulation of HO-1 and PDGF activity in hESC. As defective hESC decidualisation causes infertility and pregnancy disorders, further investigation of HO-1 up-regulation and PDGF responsiveness in decidual hESC may identify new pathways underpinning these conditions.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Award Type: | Doctorates > Ph.D. | |||||||||
| Supervisor(s): |
|
|||||||||
| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | Institute of Cardiovascular Sciences | |||||||||
| Funders: | Other | |||||||||
| Other Funders: | Ministry of Health / Iraq | |||||||||
| Subjects: | R Medicine > RZ Other systems of medicine | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/10137 |
Actions
 |
Request a Correction |
 |
View Item |
Downloads
Downloads per month over past year