Apoptotic pathways in ovarian surface epithelium of human embryos during embryogenesis and carcinogenesis: Close relationship of developmental plasticity and neoplasm

Cell differentiation and different pathways of cell death were immunohistochemically analyzed in ovaries of six human embryos, 20 serous borderline tumors (SBT) and ovarian serous carcinomas (OSC) using markers for apoptosis (caspase-3, AIF, TUNEL) and stemness (Oct-4). In the 5–8-week ovaries, caspase-3 was absent in the ovarian surface epithelium (ose) and mildly positive in the ovarian stroma (os), AIF was expressed moderately, while Oct-4 expression gradually decreased during that period. Some ovarian cells expressed only caspase-3 or AIF together with TUNEL, while both caspase-3 and AIF were co-expressed in other ovarian cells. Mild expression of Oct-4 and caspase-3 characterized some cells of SBT, while their expression varied from mild to strong in OSC. AIF displayed mild to strong expression in ose of SBT and moderate to strong expression in OSC, while no expression of AIF was observed in os of both tumors. In the ose of both SBT and OSC, caspase-3 and AIF were co-expressed only occasionally, while AIF and Oct-4 were co-expressed strongly. Our study showed the presence of stemness cells and different pathways of cell death (caspase-3 and AIF-mediated) in the ovarian tissue during development and carcinogenesis, indicating the correlation between developmental plasticity in human embryonic ovaries and OSC.