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Regulated expression of cadherin-6 and cadherin-11 in human and baboon (Papio Anubis) endometrium

University of British Columbia

The human endometrium undergoes extensive proliferation and differentiation during the menstrual cycle. To date, the molecular mechanisms involved in the cyclic remodeling of the endometrium remain poorly characterised. The cadherins are a large family of integral membrane glycoproteins which mediate calcium-dependent cell adhesion and play a central role in the formation and organisation of tissues during development. We have recently determined that the two novel cadherin subtypes, cadherin-6 and cadherin-11, are present in the human endometrium. In view of these observations, we have examined the spatiotemporal expression of these two cadherin subtypes in this complex tissue. Cadherin-6 and cadherin-11 are expressed in the glandular epithelium during the proliferative phase. The expression of epithelial cadherin-6 declines as the cycle enters the secretory phase, whereas cadherin-11 levels in the glandular epithelium remain constant throughout the menstrual cycle. In contrast, these two cadherin subtypes are differentially expressed in the endometrial stroma. Cadherin-6 is only expressed in the proliferative endometrial stroma. The loss of cadherin-6 expression in the stroma cells during the secretory phase is concomitant with an increase in the levels of cadherin-11. As the switch between cadherin- 6 and cadherin-11 in the endometrial stromal occurs when these cells are undergoing progesterone-mediated cellular differentiation, we examined the ability of this gonadal steroid to regulate these two endometrial cadherin subtypes in isolated endometrial stroma cells. Progesterone was capable of differentially regulating cadherin-6 and cadherin-11. In addition, we failed to detect cadherin-11 expression in endometrial biopsies obtained from women with habitual abortion associated with luteal phase deficiency, suggesting that cadherin-11 may play a central role in the functional maturation of the endometrium. Finally, we have localised these two cadherin subtypes in the baboon uterus in order to determine whether this non-human primate will serve as a suitable model in which to examine the role of cadherin-6 and cadherin-11 in implantation-related processes. The spatiotemporal expression of cadherin-6 and cadherin-11 in the human and baboon endometrium is similar. Collectively, these observations suggest that the two cadherin subtypes, cadherin-6 and cadherin-11, play a central role in the cyclic remodeling of the human endometrium in preparation for the implanting embryo.

Thesis/Dissertation

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2009-03-25

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http://hdl.handle.net/2429/6500

Reproductive and Developmental Sciences

University of British Columbia

UBCV

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