(598) Disrupted SERPINA1 Expression in Trophoblast of Patients with Adherent Placentation

Alpha 1 Antitrypsin (A1AT) is a protease inhibitor encoded by SERPINA1 gene and may contribute to abnormal placentation as demonstrated by increased syncytialization following knockout in cytotrophoblast as previously published from primary trophoblast research. This study aims to assess SERPINA1 expression by immunohistochemistry (IHC) on placental samples from histologically confirmed cases of placenta accreta spectrum (PAS).  

Study Design:

Archived placental specimens in paraffin-embedded blocks were studied. The specimens were from patients without PAS, adherent (Stage 2 basal plate myometrial fibers [BPMF} and Grade 1) placentation and severely adherent (Grade 2 and 3) placentation. Specimens were studied with IHC to assess SERPINA1 expression and localization.  Immunostained slides were scanned using a Zeiss Axioscan and semiquantitative scoring (–, +, ++, +++) was performed in the following cell types: extravillous trophoblast, syncytiotrophoblast, cytotrophoblast, villous fibroblast, and endothelium.   ANOVA and Fischer’s exact test were used to compare patient characteristics. Linear regressions were used to model the relation between placentation (no PAS, adherent or severely adherent), cell count and SERPINA1 expression.    

Results:

SERPINA1 expression in cytotrophoblast cytoplasm correlated negatively with adherent placenta (coefficient=-0.31 (0.15); 95% confidence interval=0.62, -0.01; p= .001). There was no such relationship for syncytiotrophoblast, extravillous trophoblast, villous fibroblast or endothelium.

Conclusion:

Current theories for PAS etiology differ, one implies an invasive trophoblast etiology while the other implies maternal disease typically attributed to prior uterine scarring.  Our findings suggest A1AT downregulation in the cytoplasm of cytotrophoblasts is associated with adherent placentation.  This is consistent with previous observation that A1AT dysfunction is linked with abnormal placental formation and may result in increased syncytialization of the cytotrophoblast, increase in placental mass, and expression of inflammatory cytokines.