Spatial and Temporal Ontogenies of Glutathione Peroxidase and Glutathione Disulfide Reductase During Development of the Prenatal Rat

Abstract

Spatial and temporal expression and regulation of the antioxidant enzymes, glutathione peroxidase(GSH-Px), glutathione disulfide reductase (GSSG-Rd) may be important in determining cell-specificsusceptibility to embryotoxicants. Creation of tissue-specific ontogenies for antioxidant enzyme activities during development isan important first step in understanding regulatory relationships. Early organogenesis-stage embryos were groupedaccording to the somite number (GD 9–13), and fetuses were evaluated by gestational day (GD 14–21). GSH-Px activities in thevisceral yolk sac (VYS) increased on consecutive days from GD 9 to GD 13, representing a 5.7-fold increase during this period of development. GSH-Pxactivities in VYS decreased after GD 13, ultimately constituting a 37% decrease at GD 21. Head, heart, and trunk specific activities generallyincreased from GD 9 to GD 13 albeit not to the same magnitude as detected in the VYS. GSSG-Rd activities showed substantial increases in the VYS from GD 9 to GD13, 6.3-fold and decreased thereafter to 50% by GD 21. The greatest changes in enzyme activities were noted in the period between GD 10 and GD 11,where the embryo establishes an active cardiovascular system and begins to convert to aerobic metabolism. Generally, from GD 14–21, embryonic organGSH-Px and GSSG-Rd activities either remained constant or increased as gestation progressed. These studies suggest the importance of the VYS in dealing withROS and protecting the embryo. Furthermore, understanding the consequences of lower antioxidant activities during organogenesis may help to pinpoint periods ofteratogenic susceptibility to xenobiotics and increased oxygen. © 2001 John Wiley & Sons, Inc. J Biochem Mol Toxicol 15:197–206, 2001