Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

Nevertheless, during the first half of egg-laying period (day 1 to day 2), the egg production was markedly reduced in mock and Gi C. elegans compared with untreated control (72% of mock control, P ¼ 0.013 and 67% of Gi control, P ¼ 0.022, respectively), whereas no significant difference was found in the second half of egg-laying period (day 3 to day 4). Remarkably, at 10mM H 2 O 2 , the total egg production was significantly reduced in both mock and Gi C. elegans compared with untreated control (65% of mock control, P ¼ 0.010 and 62% of Gi control, P ¼ 0.028, respectively). From day 1 to day 2, the egg production was severely decreased in mock and Gi C. elegans compared with untreated control (34% of mock control, P ¼ 0.001 and 38% of Gi control, P ¼ 0.001, respectively), whereas there was no significant difference in the second half of egg-laying period (day 3 to day 4). Taken together, these data indicate that high oxidative stress could be associated with G6PD knockdown-induced germ cell apoptosis and reduced egg production. Other possible mechanisms of defective egg production induced by G6PD knockdown in C. elegans. In order to elucidate the signaling pathway associated with defective egg production caused by G6PD deficiency, loss-of-function mutants of possible pathways were analyzed for their egg production. It has been shown that p53 protein expression is upregulated in oxidant-treated G6PD-deficient human fibroblasts. 11 Likewise, Gi C. elegans showed enhanced CEP-1 (p53) protein expression (1.37-fold, Figure S1 ). However, cep-1 mutation neither affected egg production (P ¼ 0.313, n ¼ 70) nor prevented G6PD knockdown-induced defective egg production in C. elegans (P ¼ 0.622, n ¼ 70) (Figure 6a ), indicating that reduced egg production caused by G6PD deficiency is independent to cep-1.