Pathomorphologic and immunohistochemical study on the devastation of rat embryos by antiphospholipid antibody positive serum.

PROBLEM: While relying on previous publications, our aim was to examine the morphologic changes, induced in early rat embryos by intra-uterine exposure to the low-molecular weight fraction of boiled human serum containing antiphospholipid antibodies (APLA) that had been obtained from women with antiphospholipid syndrome (APS). METHOD OF STUDY: Human APLA-positive sera were pooled, boiled, centrifuged and separated by ultrafiltration. The molecular weight fraction lower than 30 kDa was used for the experiments. One hundred and fifty microlitres was injected into one uterine horn of 12 pregnant rats, 5 or 6 days after fertilization, while similarly prepared normal human serum or saline were injected into the contralateral horn. The rats were subsequently sacrificed. Serial sections, obtained from all uterine horns, were stained histologically and immunohistochemically. Normal embryos developed in the control uterine horns, while embryos in the experimental horns were destroyed rapidly. RESULTS: Signs of apoptosis appeared 2 hr following the injection, and 4 hr later all the embryonic cells were apoptotically destroyed. There was only partial damage to cytotrophoblasts and intermediate trophoblasts. CONCLUSION: These findings support the existence of a novel factor in the APLA-positive serum, causing a detrimental effect to the conceptus, without any relation to the antiphospholipid antibodies.

The placental barrier in allogenic immune conflict in spontaneous early abortions: immunohistochemical and morphological study.

PROBLEM: Morphologic changes in the placental barrier in spontaneous early abortions under the maternal-embryonic immune conflict, and the role of maternal immunoglobulins (Igs) in these changes. MATERIALS AND METHODS: We examined chorionic villi and other tissues obtained from 54 aborts between weeks 3.5 and 8 of pregnancy. Material was divided into two groups. Group 1 (control) contained 15 medically recommended and spontaneous early aborts with no signs of inflammations or pathologic immune processes. Group 2 contained 39 spontaneous early aborts with acute chorionic villitis. Immunohistochemical and morphometric methods were used to study the Igs, different types of immunocompetent cells, and apoptosis-related components of the placental barrier. RESULTS: Acute villitis was found to be characterized by the destruction of all components of the chorionic villi, thrombovasculitis with apoptosis of the endothelium of capillaries and erythroblasts, mucous swelling of the basal membrane, and coagulation of the blood proteins. Due to destruction of the capillaries, the number of avasculate villi increased, and the average number of capillaries per villus decreased. The extremely high number of phagolysosomes with IgG and IgA in the villous monocytes in the group 2 indicates an increase in the phagocytic activity of monocytes against maternal Igs and may reflect the presence of mother-embryo immune conflict. Apoptosis of monocytes and a high number of promonocytes were seen accompanied by a high concentration of p53 protein. A large disturbance in the trophoblast occurred with disappearance of bcl-2 and the appearance of Fas ligand. CONCLUSION: Massive destruction of maternal Igs in embryonic monocytes and acute villitis in the placental barrier are manifested during the mother-embryo immune conflict, and this may be one of the reasons of spontaneous early abortions.