Determination of the transcript profiles of human endometrium and endometriosis

The human endometrium is a complex tissue that undergoes an idealised 28-day cycle, strictly controlled by the ovarian steroid hormones. Endometriosis is a common disease affecting 10% of all women of reproductive age. It is characterised by severe abdominal pain, and can result in infertility. Current treatment strategies for this disease are insufficient. In this study, I determine the transcript profiles of normal human endometrium and endometriosis, in the hope that they may lead to improved treatments for this debilitating disease. I use microarray technology to determine the levels of tens of thousands of transcripts in a range of endometrial samples. Through the application of a range of sophisticated statistical techniques, specifically designed for the analysis of extensive microarray data sets, I identify transcripts that are present at significantly different levels in eutopic endometrium, from women with and without endometriosis, and in peritoneal ectopic endometriotic lesions. I discover a number of transcripts that have not previously been identified in either the endometrium or endometriosis, and report three new factors that may be important in the correct cycling of the endometrium or in the pathology of endometriosis. I propose that glutathione peroxidase 3 is required in the endometrium during the secretory phase of the menstrual cycle to protect implanting blastocysts from free radical damage. I suggest that intestinal trefoil protein TFF3 may be required for the correct remodelling of the endometrium following menstruation, and I implicate the transcription factor four and a half LIM domains 1 in the establishment of endometriotic lesions at ectopic sites. These findings offer novel insights into the regulation of the endometrium and its potential pathologies. The identification of these new transcripts in the endometrial system are a step towards the development of improved treatments for endometriosis.