Developmental patterns of zygotes from transgenic female mice with elevated tissue glutathione

Zygotes were collected from transgenic mice overexpressing glutathione synt hetase to test the hypothesis that such zygotes are more capable of develop ing in suboptimal culture media than zygotes from non-transgenic (control) mice. The effects of injection of donor mice with gamma-glutamylcysteinyl e thyl ester (gamma-GCE) on embryonic development were also investigated. In addition, the effects of genetic background (i.e., transgenic vs. non-trans genic) and injection with gamma-GCE on developmental capacity in kSOM were studied after exposure of zygotes to diamide (0.01 mM, for 30 min). When cu ltured in modified Medium 16 significantly more pronuclear ova from transge nic females reached the morula (M) and early blastocyst (EB) stages than em bryos derived from control mice. Genetic background significantly affected the proportions of embryos reaching 4- to 16-cell, NI and EB stages during culture in modified Whitten's medium (WM); more zygotes collected from tran sgenic than from control mice developed. The injection of experimental mice with I-GCE significantly increased proportions of zygotes developing to M and EB stages in WM. Following exposure to diamide and subsequent culture i n kSOM significantly more zygotes collected from transgenic mice reached th e 4- to 16-cell stages than those from control females; a significant posit ive effect on developmental capacity was also seen after injection of donor mice with gamma-GCE. When cultured in suboptimal conditions, zygotes deriv ed from transgenic mice overexpressing glutathione synthetase were more cap able of developing than zygotes of nontransgenic control females. Zygotes f rom the transgenic mice also exhibited greater capacity to withstand toxic exposure to diamide. Present data suggest that commonly known strain differ ences in preimplantational development in vitro may reflect differences in the synthesis and/or metabolism of glutathione. (C) 2000 Wiley-Liss, Inc.