Glucose 6-phosphate dehydrogenase (G6PD) deficiency, known as favism, is 
classically manifested by hemolytic anemia in human. More recently, it has been 
shown that mild G6PD deficiency moderately affects cardiac function, whereas 
severe G6PD deficiency leads to embryonic lethality in mice. How G6PD deficiency 
affects organisms has not been fully elucidated due to the lack of a suitable 
animal model. In this study, G6PD-deficient Caenorhabditis elegans was 
established by RNA interference (RNAi) knockdown to delineate the role of G6PD 
in animal physiology. Upon G6PD RNAi knockdown, G6PD activity was significantly 
hampered in C. elegans in parallel with increased oxidative stress and DNA 
oxidative damage. Phenotypically, G6PD-knockdown enhanced germ cell apoptosis 
(2-fold increase), reduced egg production (65% of mock), and hatching (10% of 
mock). To determine whether oxidative stress is associated with G6PD 
knockdown-induced reproduction defects, C. elegans was challenged with a 
short-term hydrogen peroxide (H2O2). The early phase egg production of both mock 
and G6PD-knockdown C. elegans were significantly affected by H2O2. However, 
H2O2-induced germ cell apoptosis was more dramatic in mock than that in 
G6PD-deficient C. elegans. To investigate the signaling pathways involved in 
defective oogenesis and embryogenesis caused by G6PD knockdown, mutants of p53 
and mitogen-activated protein kinase (MAPK) pathways were examined. Despite the 
upregulation of CEP-1 (p53), cep-1 mutation did not affect egg production and 
hatching in G6PD-deficient C. elegans. Neither pmk-1 nor mek-1 mutation 
significantly affected egg production, whereas sek-1 mutation further decreased 
egg production in G6PD-deficient C. elegans. Intriguingly, loss of function of 
sek-1 or mek-1 dramatically rescued defective hatching (8.3- and 9.6-fold 
increase, respectively) induced by G6PD knockdown. Taken together, these 
findings show that G6PD knockdown reduces egg production and hatching in C. 
elegans, which are possibly associated with enhanced oxidative stress and 
altered MAPK pathways, respectively.