Extracellular matrix (ECM) remodeling accompanies cell migration, cell--cell interactions, embryo expansion, uterine implantation, and tissue invasion during mammalian embryogenesis. We have found that mouse embryos secrete functional ECM-degrading metalloproteinases, including collagenase and stromelysin, that are inhibitable by the tissue inhibitor of metalloproteinases (TIMP) and that are regulated during peri-implantation development and endoderm differentiation, mRNA transcripts for collagenase, stromelysin, and TIMP were detected as maternal transcripts in the unfertilized egg, were present at the zygote and cleavage stages, and increased at the blastocyst stage and with endoderm differentiation. These data suggest that metalloproteinases function in cell-ECM interactions during growth, development, and implantation of mammalian embryos.

Naturally occurring antiphospholipid antibodies are strongly associated with placental dysfunction and severe obstetrical complications. We have produced three monoclonal antiphospholipid antibodies that differentiate between phosphatidylserine (PS)- and cardiolipin (CL)-dependent antigens, 3SB9b (CL-/PS+), BA3B5C4 (CL+/PS+), and D11A4 (CL+/PS-). We tested these monoclonal antiphospholipid antibodies in an assay for intertrophoblastic fusion. A JAR choriocarcinoma cell line was induced to undergo intercellular fusion by forskolin in the presence or absence of monoclonal antiphospholipid antibodies. The amount of syncytium formation was quantified by using fluorescein isothiocyanate (FITC)-conjugated anti-desmosome antibody to visualize intercellular membranes and propidium iodide to stain nuclei and by counting those cells with multiple nuclei. Without the presence of antiphospholipid antibodies, and in cultures containing BA3B5C4 (CL+/PS+) or D11A4 (CL+/PS-), approximately 70% of JAR formed syncytial cells after 24 h of forskolin treatment. Less than 13% of the cells formed synctia in 2-day cultures that were not exposed to forskolin or that contained forskolin in the presence of 3SB9b (CL-/PS+). These data suggest that phosphatidylserine is externalized during intertrophoblastic fusion and that antiphospholipid antibody with reactivity against PS, but not CL, can affect placental development by interfering with the normal formation of syncytiotrophoblast.

From 15 to 20% of the RNA of virulent strains of poliovirus is degraded at 35 °C several hours after maximal synthesis is reached. From 20 to 30% of the RNA of attenuated viruses is degraded under the same conditions. Cultures placed at 40 °C in the presence of 3 mM guanidine during the linear stage of RNA synthesis lead to breakdown of 15 to 40% of the RNA of virulent viruses and 30 to 40% of the RNA of attenuated viruses. It is doubtful that breakdown of RNA alone can explain the temperature sensitivity of attenuated viruses.

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