DEVELOPMENTAL EXPRESSION OF EXTRACELLULAR GLUTATHIONE-PEROXIDASE SUGGESTS ANTIOXIDANT ROLES IN DECIDUUM, VISCERAL YOLK-SAC, AND SKIN

Extracellular glutathione peroxidase (EGPx) is a secreted selenium-dep endent enzyme that reduces hydroperoxides and organic hydroperoxides. Selenium deficiency in females is associated with infertility and spon taneous abortion, suggesting a role for selenium-requiring proteins du ring embryonic development. To gain insight into functions of EGPx in vivo, we determined sites of murine EGPx synthesis by in situ hybridiz ation during embryogenesis and in adult tissues. At E7.5 of developmen t, high EGPx expression was found in the maternally derived deciduum, with lower levels of accumulation in the embryonic visceral endoderm. At E9.5, the major sites of expression were the yolk sac endoderm and heart musculature, By E16.5, EGPx mRNA expression persisted in yolk sa c endoderm but also accumulated significantly in atrially derived myoc ytes, ossification centers, adipose tissue, intestinal epithelium, and in a ventral-to-dorsal gradient in developing skin. Glutathione perox idase activity due to EGPx protein was identified in the fluids surrou nding the developing mouse embryo at midgestation. The expression of E GPx in tissues at the maternal-fetal interface-deciduum, visceral yolk sac, and skin-suggests that EGPx may serve to protect the embryo from oxidant damage. In adult mice, we identified the S1 segment of the ki dney proximal tubules as the primary site of EGPx mRNA accumulation, w ith lower EGPx levels in atrial cardiac muscle, intestine, skin, and a dipose tissue. These findings suggest that EGPx may serve a wider anti oxident role than previously recognized in the interstitium of multipl e localized tissues, particularly those associated with the active tra nsport of lipids. (C) 1998 Wiley-Liss, Inc.