Mechanics and extracellular matrix in the mouse ovary
File(s)
Author(s)
Hopkins, Thomas
Type
Thesis or dissertation
Abstract
The extracellular matrix (ECM) is a 3-D non-cellular network of components found across all tissues and cells. It acts as a supportive scaffold and regulates several processes at the cellular and tissue level. Additionally, structural properties of the ECM defines a tissues overall mechanical characteristics. Perturbations in this environment are linked with a number of pathologies. In the ovary, the ECM participates in various processes key to the development of competent follicles capable of fertilisation. Histological analysis of ovaries from women with Polycystic Ovary Syndrome (PCOS), demonstrate structural changes in the ECM, including stromal hyperplasia and fibrotic thickening. Results shown here, demonstrated the alteration of several ECM and matrix-associated components in women with PCOS. This thesis outlined the structural characterisation of several of these components within the mouse ovary. Furthermore, evidence suggests that follicles respond to the mechanical properties of their environment, however, little is known about the mechanical properties of the ovary itself. Evidence presented within this thesis demonstrated, for the first time, the unique mechanical characteristics of the mouse ovary, which displays clear heterogeneity and distinct microenvironmental variation. A common feature of PCOS is excess androgen production. To explore the effect of androgen exposure on the ovarian ECM, mouse follicles and ovarian fragments were treated with androgens in vitro. These experiments revealed changes in a number of key structural and matrix-related genes, which have implications in the development of fibrosis, basal lamina structure and mechanotransduction. Moreover, analysis of components of the Hippo signalling pathway highlighted increased activity of this key mechanotransductive pathway. Equally, increases were seen in members of the transforming growth factor Beta (TGFB) pathway, implicated in tissue fibrosis and matrix deposition. Altogether this work provides insight on the unique mechanical and structural properties of the mouse ovarian environment, with further work implicating changes altered within PCOS.
Version
Open Access
Date Issued
2021-05
Date Awarded
2021-12
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Dunlop, Iain
Hardy, Katharine
Sponsor
Engineering and Physical Sciences Research Council
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)