Differential expression of angiopoietin-1, angiopoietin-2, and Tie receptors in placentas from pregnancies complicated by placenta accreta

ObjectiveThe purpose of this study was to investigate the differential expression of angiopoietin-1, angiopoietin-2, and Tie receptors (Tie-1 and Tie-2) in placentas from pregnancies complicated by placenta accreta.Study designParaffin sections of 46 placental specimens with (cases) and 46 without (controls) placenta accreta were studied immunohistochemically for the expression of Tie receptors and angiopoietin-2 in trophoblast populations. Protein levels of Tie receptors and angiopoietins were also examined by Western blot analysis and/or enzyme-linked immunosorbent assay. Controls were matched for gestational age in this case-control study.ResultsIn both second and third trimesters, the percentage of intermediate/strong immunoreactivity of Tie-2 in the syncytiotrophoblast was significantly lower in cases than controls (P = .015 and .025, respectively). However, Tie-2 expression in the cytotrophoblastic and extravillous trophoblastic cells and Tie-1 in all trophoblast subpopulations were not significantly different between cases and controls (P > .05). The majority of Tie-2 expression, as demonstrated by Western blots, was consistent with the trends of immunohistochemical findings in the syncytiotrophoblast. Enzyme-linked immunosorbent assay in the placental lysates showed that women with placenta accreta demonstrated significantly higher angiopoietin-2 and lower Tie-2 concentrations than did women with normal pregnancies (P = .026 and .003, respectively). Placental angiopoietin-1 levels did not have any significance (P > .05). Also, angiopoietin-2 immunoreactivity in the syncytiotrophoblast was compatible with the finding demonstrated by enzyme-linked immunosorbent assay (P = .005 and .012, respectively).ConclusionThese observations suggest that the participation of up-regulated angiopoietin-2 and down-regulated Tie-2 in the placental tissues may indicate a role for these angiogenic factors in the development of placenta accreta.