255: The degree of expression of serine protease HtrA1 and its affects on trophoblast cell invasion in normal and abnormal placentation


      Previous work by Ajayi et al demonstrated that serine protease HtrA1 (high temperature requirement factor A1) is overexpressed in trophoblastic tissue in severe preeclamptic women and limits the degree of migration and invasion of trophoblast cells. We hypothesize that aberrant expression of HtrA1 may play a role in pregnancies complicated by placenta accreta, increta or percreta.

      Study Design

      All women who underwent cesarean/postpartum hysterectomy at Mayo Clinic were identified over a 15 year period. Tissue blocks from the placental-uterine interface were immunohistochemical stained with affinity-purified anti-HtrA1 antibody as previously described. The level of HtrA1 expression was quantitatively scored via light microscopy by a placental pathologist blinded to the clinical history and assigned a ranking score of 0 (no staining) to 3 (marked staining). A similar preparation was performed by Ajayi et al analyzing specimens of women with severe preeclampsia for comparision. Fischer′s Exact test was performed with statistical significance defined as p<0.05.


      Fourteen patients underwent hysterectomy for abnormal placentation (accreta-6, increta-4, percreta-4) while twenty patients underwent hysterectomy for other conditions. When HtrA1 expression in accreta, increta or percreta group was compared to those of the preeclampsia group, the difference was statistically significant for villous (p=0.0258) and extravillous (p=0.0026) trophoblastic samples. However, when comparing samples from the normal placentation group to the accreta, increta or percreta or preeclampsia group, no difference was found.


      Our results suggest that underexpression of HtrA1 in villous and extravillous trophoblasts may be responsible for the excessive depth of invasion in pregnancies complicated by placenta accreta, increta, or percreta. In fact, one can view these findings as part of the continuum or spectrum of disease severity with HtrA1 overepression resulting in shallow trophoblast invasion in preeclampsia and underexpression in cases of abnormally adherent invasion.