G6PD lactylation is involved in regulating redox balance of boar sperm in low glucose extender

Abstract

Glucose metabolism is an essential pathway that indirectly supports cellular redox homeostasis by providing reducing equivalents, such as NADPH, particularly in the highly specialized sperm. Sperm exhibit higher progressive motility in low glucose extender. However, the underlying mechanisms remain unclear. The objective of the present study was to investigate effect of low glucose on sperm metabolism and lactylation modification. After 3 h of incubation, low glucose had an effect on the redox state of boar semen in vitro, particularly in terms of the concentration of reactive oxygen species (ROS) and reductive products. Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was significantly increased at low glucose condition, accompanied by increased lactate accumulation extracellularly. Meanwhile, protein lactylation levels were enhanced, with G6PD identified as one of lactylation proteins. In conclusion, low glucose incubation induced lactylation of G6PD, resulting in increased enzymatic activity that enhanced the pentose phosphate pathway (PPP), which in turn increased antioxidant capacity and maintained sperm motility in a low glucose environment. The research results provide valuable insights into the adaptation mechanisms of sperm to their environment and offer new perspectives and opportunities for reproductive biology research.