The immunohistochemical distribution of superoxide dismutase (SOD) was examined in the human endometrium throughout the menstrual cycle. Surface and glandular epithelia showed positive staining throughout the menstrual cycle except just prior to the menstruation.Staining activity was more intense in the cytoplasm than that in the nucleus. Specific immunostaining of SOD was demonstrated in sub-and supranuclear vacuoles of glandular epithelia, and intraglandular substances during the early and mid secretory phases; i.e., the preand peri-implantation periods. Meanwhile, stromal cells showed weaker staining activity than surface and glandular epithelia throughout the menstrual cycle until the 22th day. Once the predecidual change occurred in stromal cells on the 23th day, predecidual cells came to show intensive staining. However, specific staining was shown neither in predecidual cells nor in surface or glandular epithelia just prior to the menstruation. In addition, SOD activity was also shown in the decidual cells of 8 weeks gestation and in the reserve cells of the endocervix. Collectively, the present immunohistochemical recults suggest that SOD may play an important role not only in the protection of developing embryos from superoxide anion radicals but also in the local defense mechanism against tissue damages resulting from inflammation in the uterine cavity, and that the expression of SOD may be regulated by sex steroids, especially progestorone. Furthermore, SOD could be a useful indicator to clinically diagnose the degree of predecidualization and the luteal phase defect.The superoxide anion, a free radical generated during the monovalent metabolic reduction of oxygen, is toxic to the aerobic cell in which it is produced (13). The superoxide anion radical has been reported to damage cell membrane (22) and DNA (35), and to inactivate various enzymes (6). Also, it has been implicated in a variety of pathologic processes, including diabetes mellitus (11), lung damage (20), hepatitis (36), myocardial reperfusion injury following surgery (16), cataract (4), and so on. Therefore, effective detoxication of the superoxide anion radical appears to be a prerequisite for life in an oxygen-containing environment. Superoxide dismutase (SOD), known as superoxide oxidoreductase is an enzyme that catalyzes the dismutation (reduction/oxidation) of the superoxide anion radical in the following reaction: 2H+ +202 --k H202+02, and it is important as a biological defense mechanism against 487 488 Narimoto et al.cell injury mediated through superoxide anion radicals (12). In mammalians, three types of SOD have been identified which have different structures and metal contents: a cytoplasmic copper-zinc SOD (CuZn-SOD) (26), a mitochondrial manganese SOD (Mn-SOD) (3) and an extracellular SOD of high molecular weight (EC-SOD) (23).Mammalian preimplantation embryos grown in vitro are likely to exhibit sub-optimal or retarded development (45). In rodents, for example, the 2-cell block phenomenon, i.e., the proliferation arrest of f...