Expression of adhesion molecules in first trimester spontaneous abortions and their role in abortion pathogenesis

Early placental development is associated with complex regulatory mechanisms, and molecular communication problems that arise during the developmental process are dangerous for continuation of the pregnancy. As studies on the process of invasion and migration of trophoblast cells have shown the importance of cell-cell and cell-matrix interactions, we examined the effects of adhesion molecules on the mechanism(s) of spontaneous abortions and compared them to elective abortion materials using histopathological and immunohistochemical methods. To the best of our knowledge, this is the first study to investigate adhesion molecules in spontaneous abortions.

Curettage materials from abortions were examined retrospectively in the Department of Pathology, Zonguldak Karaelmas University School of Medicine, Zonguldak, Turkey. CD31/PECAM-1 (endothelial cell marker), CD44v (variant 3), E-cadherin, CD54/ICAM-1, and CD106/VCAM-1 expression profiles were evaluated by immunohistochemistry, and cellular localization was determined under light microscopy. The results of spontaneous abortions were compared to those of elective abortions.

The staining percentages of CD31, CD44, CD106, and E-cadherin decreased in cases of spontaneous abortion, but CD54 (ICAM-1) expression increased. Statistically significant differences were detected between spontaneous and elective abortion materials with regard to cytotrophoblasts (CTs), syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs) with the anti-CD31 antibody (p=0.0001). In addition, CD54 (p=0.007 and p=0.002) and E-cadherin (p=0.002 and p=0.02) expression in CTs and STs, respectively, were significantly different. Furthermore, CD44 expression (p=0.003) in decidual (D) cells and CD106 (p=0.0001) expression in vessels of endometrial (E) and villous tissues were also significantly different.

Decreased CD31 expression in CTs that invade the spiral arterioles and mimic E cells in spontaneous abortion cases suggests that CD31/PECAM-1 is an important molecule in uteroplacental adequacy. Moreover, diminished expression of CD44 in D cells caused impaired stroma-villous connections. Enhancement of ICAM-1 in placental and invading STs may be useful as a diagnostic marker for patients who may have a tendency to have spontaneous abortions. A down-regulation of E-cadherin was observed, which may be responsible for impaired CT differentiation and loss of the pregnancy. Furthermore, decreased VCAM-1 expression in spontaneous abortions may be consistent with the importance of VCAM-1 in trophoblast-endothelial cell interactions. Many adhesion molecules are known to be effective in the normal development of a pregnancy, and the analysis of adhesion molecules in spontaneous abortions will provide useful information for clarifying the physiopathology of spontaneous abortions.