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.Medicine, Faculty ofObstetrics and Gynaecology, Department ofGraduat
