The placenta as a chimeric organ?

Ziel: The mechanisms that allow a woman to immunologically tolerate pregnancy remain enigmatic. Askewed tolerance is associated with pregnancy pathologies, e.g. miscarriage and preeclampsia. Especially the behavior of first trimester trophoblasts is intriguing: they invade the decidua while evading the uterine immune system, similar to malignancies, with the goal of replacing spiral artery endothelium with endovascular trophoblast.Fetomaternal microchimerism has emerged recently as a possible means of inducing tumor cell tolerance. Also, new investigations give cause to believe that trophoblast fuse with maternal endothelial cells, thus creating a new chimer. Defining this process might help to understand pregnancy tolerance better.

Methodik: The distribution of the fusiogenic proteins, ADAM12 (A Disintergrin and Metalloproteinase 12) and dysferlin, were examined immunohistochemically. The same probes were co-marked with a trophoblast-specific antibody to validate co-localization of the protein in trophoblasts. Trophoblastic and endothelial cell lines were stained respectively with MitoTracker red and green and then co-incubated in an in vitro model of confrontation. Fusion events are demarcated as yellow, multinucleate cells under a fluorescence microscope.

Ergebnis: Both fusiogenic proteins are syncytially expressed at known fusion prone areas. The proteins are also expressed in trophoblasts surrounding decidual vessels. The pattern of dysferlin expression in fused, syncytiotrophoblast (line-formed, near cell membrane) is lost in non-fused, extravillous trophoblasts (ubiquitary in cell plasma). In endovascular trophoblast, the line formation reappeared. In vitro, putative fusion events were registered.

Schlussfolgerung: The expression of fusiogenic proteins in endovascular trophoblast suggest the capacity of these cells to fuse (with maternal endothelia). In an in vitro model, chimeric fusion events seem apparent. Genetic investigations are underway to validate this notion.

chimer - chimeric - endothelium - fusion - placenta - trophoblast