Developmental expression of extracellular glutathione peroxidase suggests antioxidant roles in deciduum, visceral yolk sac, and skin.
Extracellular glutathione peroxidase (EGPx) is a secreted selenium-dependent enzyme that reduces hydroperoxides and organic hydroperoxides. Selenium deficiency in females is associated with infertility and spontaneous abortion, suggesting a role for selenium-requiring proteins during embryonic development. To gain insight into functions of EGPx in vivo, we determined sites of murine EGPx synthesis by in situ hybridization during embryogenesis and in adult tissues. At E7.5 of development, 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 sac endoderm but also accumulated significantly in atrially derived myocytes, ossification centers, adipose tissue, intestinal epithelium, and in a ventral-to-dorsal gradient in developing skin. Glutathione peroxidase activity due to EGPx protein was identified in the fluids surrounding the developing mouse embryo at midgestation. The expression of EGPx 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 kidney proximal tubules as the primary site of EGPx mRNA accumulation, with lower EGPx levels in atrial cardiac muscle, intestine, skin, and adipose tissue. These findings suggest that EGPx may serve a wider antioxidant role than previously recognized in the interstitium of multiple localized tissues, particularly those associated with the active transport of lipids.
Kingsley
P D
PD
Department of Pediatrics and Cancer Center, University of Rochester Medical Center, New York 14642, USA.
Whitin
J C
JC
Cohen
H J
HJ
Palis
J
J
D000653:Amniotic Fluid / Q000201:enzymology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation; D003656:Decidua / Q000196:embryology / Q000201:enzymology*; D005110:Extracellular Space / Q000201:enzymology*; D005260:Female; D005979:Glutathione Peroxidase / Q000096:biosynthesis*; D007668:Kidney / Q000201:enzymology / Q000254:growth & development; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012867:Skin / Q000196:embryology / Q000201:enzymology*; D018243:Teratocarcinoma / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured; D015017:Yolk Sac / Q000196:embryology / Q000201:enzymology*
D000975:Antioxidants; D012333:RNA, Messenger; D005979:Glutathione Peroxidase