Differences in phenotypic features and hormone responsiveness between healthy eutopic endometrium and tubal epithelium in women– functional relevance in gynaecological disease

Bunni, Eve (2014) Differences in phenotypic features and hormone responsiveness between healthy eutopic endometrium and tubal epithelium in women– functional relevance in gynaecological disease. Master of Philosophy thesis, University of Liverpool.

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Abstract

Introduction: We recently reported a unique phenotypic profile for the epithelial cells of the basalis compartment of the human endometrium, from where the functionalis is regenerated after menstrual shedding. As the human fallopian tube shares the same embryonic origin as the uterus and has the capacity to undergo changes according to the menstrual cycle including regeneration, we wondered whether this unique phenotype was shared with the fallopian tube. Recently it has been thought that the distal fallopian tubal mucosa may also contain a stem cell population - it was found that cells were expressing markers that were known to be stem cell markers in other tissues. This suggested that the distal mucosa may be equivalent to the stem-cell rich stratum basalis of the endometrium. Endometrial expression of steroid receptors vary throughout the menstrual cycle in response to the fluctuating steroid hormones in the circulation. Although some evidence exists on steroid receptor presence in human fallopian tube, detailed examination of both the distal and proximal parts of the tube has not been studied. Furthermore even though the androgen receptor has been identified in the human endometrium, the effect of androgens on fallopian tube and endometrial mucosa has not been studied to date. Aim: To examine the differential expression of phenotypic markers and hormone responsiveness between the endometrium and fallopian tubal epithelium in healthy women across the menstrual cycle and in the postmenopausal period. Methods: A prospective study examining 22 full-thickness endometrium and matched tubes for the basal endometrial epithelial markers (SOX9, SSEA1, nuclear β-Catenin, BCAM), Sialylated SSEA-1, Steroid receptors and the proliferative marker KI67 with immunohistochemistry and analysed using a modified-Quickscore. Secondary confirmation of data by RT-PCR. Explant cultures of matched endometrial and fallopian tube tissue (n=3) were treated with DHT for 24 hours and expression of SOX9, AR and Ki67 was assessed with IHC/RT-PCR. Main results: Trends were observed in the sample populations. The proliferative activity and phenotypic marker expression of distal tubal epithelium correlated with that of the endometrial basalis epithelium. SSEA-1, SOX9 and cytoplasmic beta catenin increased after the menopause in both endometrial and fallopian tubal epithelia. Steroid hormonal expression however, showed a unique pattern in tubal epithelial cells which may play a role in preventing cyclical regeneration in the tube. Proximal and distal portions of the tube had different responses to ER alpha and beta throughout the menstrual cycle indicating a unique function in the isthmic region of the tube in the premenopausal population. Short-term explant culture, DHT treatment up-regulated AR expression with an increase in KI67 in tubal epithelium, but no difference was observed in the matched endometrial epithelium. Increased AR and KI67 expression was observed in the endometrial stroma. Messenger-RNA expression of SOX9 was reduced after DHT treatment. IHC results were confirmed by RT-PCR. Conclusion: The Tubal Epithelium and Endometrial Mucosa share a phenotypic profile consistent with their shared embryonic origin. Explant analysis suggests a unique role for androgens in the tube. After menopause, it is evident that the tubal epithelia and endometrial glands exist as a continuum. Proximal and distal tubal epithelia have different patterns of steroid receptor expression throughout the menstrual cycle suggesting a unique steroid hormone response in the proximal tube possibly separating these organs and preventing cyclical regeneration in the tube.

Item Type:	Thesis (Master of Philosophy)
Additional Information:	Date: 2014-08-26 (completed)
Depositing User:	Symplectic Admin
Date Deposited:	10 Feb 2015 13:10
Last Modified:	17 Dec 2022 02:11
DOI:	10.17638/02002400
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2002400