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Expression of cadherins and integrins in human endometrium throughout the menstrual cycle
P J van der Linden1, A F de Goeij, G A Dunselman
1Department of Obstetrics and Gynecology, Academisch, Ziekenhuis Maastricht, The Netherlands.
Objective:
To detect cadherin and integrin expression in biopsies of endometrium in the phases of the cycle. Cell adhesion molecules may be involved in endometrial shedding during menstruation and attachment of shed endometrial tissue to the peritoneal lining in endometriosis patients.
Design:
An immunohistochemical study on fresh frozen sections.
Setting:
Tertiary-care university medical center.
Patients:
Sixteen patients undergoing monitoring of their cycle as part of a subfertility workup. All patients had regular and ovulatory cycles.
Interventions:
Endometrium samples were obtained at well-defined phases of the cycle. Simultaneously, blood samples were collected for E2 and P assay.
Main Outcome Measures:
The expression of cell adhesion molecules, including E- and P-cadherin and the integrins alpha 2 beta 1, alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1, and the expression of estrogen receptor (ER) and P receptor (PR).
Results:
E- and P-cadherin expression was demonstrated in all endometrium samples. Integrins alpha 3 beta 1, alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1 were detected in samples from all cycle phases, whereas integrin alpha 2 beta 1 was not detected in midluteal samples. The serum levels of E2 were 24.7 pg/mL (range: 10.9 to 35.4 pg/mL) in the early follicular phase and 190.7 pg/mL (range: 152.5 to 256.1 pg/mL) in the preovulatory phase (conversion factor to SI unit, 3.671). Serum P was 13.7 ng/mL (range: 10.3 to 16.7 ng/mL) in the midluteal phase and 6.4 ng/mL (range: 1.2 to 13.7 ng/mL) in the premenstrual phase (conversion factor to SI unit, 3.180). The portion of cells staining for ER and PR was at a maximum during the preovulatory phase, both for epithelial and stromal cells.
Conclusions:
E- and P-cadherin expression was detected in all samples and did not vary throughout the menstrual cycle. If their expression is involved functionally in the cyclic menstrual shedding, the loss of expression is limited to a short period of time. Of the beta 1 integrins, only alpha 2 beta 1 expression was modulated during the menstrual cycle and found to be absent in the midluteal phase. No relation was found between the expression of cell adhesion molecules and the expression of ER and PR. Because the cadherins and beta 1 integrins could be detected in late luteal phase endometrium, these cell adhesion molecules could be involved in the attachment of endometrial fragments to the peritoneal lining as a result of retrograde menstruation. The potential function in the pathogenesis of endometriosis remains to be elucidated.