The emerging role of epigenetics in the aetiology of endometriosis.

De Montfort University Open Research Archive

Show simple item record Rosser, Matthew 2011-06-02T15:32:58Z 2011-06-02T15:32:58Z 2011
dc.description.abstract BACKGROUND. Endometriosis is a very common but poorly understood disease. Defined as the presence of tissue resembling endometrial glands and stroma found in various locations around the body the disease manifests as implants which periodically proliferate and bleed. Our understanding of the mechanisms underlying the disease is limited. No methods are available for predicting the incidence of endometriosis around the world. There are many theories concerning the origin of endometriosis that contradict and complement each other. Heritable changes in gene expression independent of changes to DNA sequence, often referred to as epigenetics, is being considered as one possible mechanism via which endometriosis can develop. Epigenetics is a relatively new field of research that has revolutionised the understanding of complex diseases such as cancer and diabetes. AIMS AND OBJECTIVES. Firstly, this thesis aims to provide a novel model for predicting the incidence of endometriosis based on known epidemiological risk factors. The second aim of this thesis is to investigate the involvement of epigenetic mechanisms such as DNA methylation, loss of imprinting and aberrant microRNA expression in the aetiology of endometriosis. METHODS. For the prediction of endometriosis, data on known epidemiological risk factors for endometriosis, including diet and parity, were collected for 121 countries from various international databases such as the Food and Agriculture Organisation and World Health Organisation, normalised and used to generate a model predicting patterns of endometriosis risk. For the epigenetic study, systematic reviews and critical analysis was carried out on the literature concerning DNA methylation and transgenerational epigenetic inheritance, as well as other epigenetic mechanisms found to be disrupted in endometriosis. Bioinformatic analysis of imprinted gene databases and microRNA prediction software was cross referenced with existing microarray data on endometriosis to identify novel imprinted genes and microRNAs that may be involved in the aetiology of endometriosis. RESULTS AND DISCUSSION. The prediction model reveals that the incidence of endometriosis is most prevalent in Northern Europe and North America, with the lowest incidences in equatorial Africa. Asia and South America appear to be areas of intermediate risk. The incidence of endometriosis, predicted from the proposed model, concurs with what limited knowledge currently exists concerning the incidence of endometriosis, based on previous epidemiological studies, suggesting that it is reliable. This preliminary model provides, for the first time, information about endometriosis prevalence outside Europe, America and Australia and presents a basis for a more detailed epidemiological investigation into endometriosis. Analysis of epigenetic data identified the v aromatase cycle and estrogen sensitivity in endometriotic cells as having an epigenetic origin. Two imprinted genes, ABS4 and BEGAIN, were identified as being disrupted in endometriosis, with the potential for epigenetic disruption of IGF-2 in endometriosis also discussed. Numerous microRNAs, such as mir-23a and mir-29a, were identified as playing a significant role in the immune system dysfunction observed in endometriosis. The evidence for environmentally induced endometriosis being transmitted to future generations by epigenetic means is also presented. CONCLUSION. A promising new approach for predicting the incidence of endometriosis has been developed that can be further developed in the future to improve its predictive accuracy and robustness. The combined bioinformatics and genomic data analysis identified aberrations in imprinted genes and microRNAs that may play a significant role in the development of endometriosis. This provides the basis for future studies exploring these systems that may provide novel therapeutic strategies for the treatment of endometriosis. en
dc.language.iso en en
dc.publisher De Montfort University en
dc.subject Endometriosis en
dc.subject Epigenetic en
dc.subject prediction en
dc.title The emerging role of epigenetics in the aetiology of endometriosis. en
dc.type Thesis or dissertation en
dc.researchgroup Reproduction Research Group
dc.publisher.department Faculty of Health and Life Sciences en
dc.type.qualificationlevel Masters en
dc.type.qualificationname MPhil en

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