Abstract

Recently preeclampsia (PE) has been linked throught molecular evidence to endoplasmic reticulum (ER) stress in the placenta. In this organ ER stress is generated due to placental oxidative stress as a consequence of malperfusion secondary to deficient spiral artery remodeling. Immunohistochemistry and ultrastructural analysis were used to study tissue specimens from 14 term placentas: 4 normal, 4 PE, 3 intrauterine growth restriction (IUGR), and 3 PE+IUGR. Antihuman Amyloid A mouse monoclonal antibody (AA) and antihuman mouse monoclonal antibody to active caspase 3 were used in the immunohistochemistry study. Ultrastructural analysis was also performed by transmission electron microscopy. We found that cytotrophoblast (CT) apoptosis was increased in presence of amyloidosis. In IUGR placentas, amyloid deposits were located on the trophoblast basal lamina and were not observed into the cytoplasm of the syncytiotrophoblast (ST); in PE amyloidosis was evidenced throughout the cytoplasm of CT and ST cells, with expulsion of ST microparticles into the maternal blood. In PE+IUGR condition, amyloid deposits were observed similar to PE but reaching as far as the fetal endothelium. Additionally we found presence of activated caspase 3 in the CT and ST of PE placentas. We propose that the degree of CT apoptosis regulates the fate of the amyloid deposits produced by ER stress in the ST. The morphological and immunohistochemical evidence provided in this work support the inclusion of PE in the group of conformational or protein misfolding diseases.

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