LDHC Hyperacetylation Disrupts the Guanidinoacetic Acid-Creatine Axis Underlying Cryoinjury in Boar Sperm: Rescue by GAA Supplementation
Abstract
Boar sperm are highly sensitive to cryopreservation, limiting the use of frozen semen in pig breeding. We previously reported that cryopreservation alters lysine acetylation of metabolism-related proteins, including the sperm-specific isoform LDHC. Here we show that cryopreservation reduces LDH activity, and that the LDH inhibitor galloflavin recapitulates this loss, confirming that LDHC is required for boar sperm motility, acrosome integrity, and mitochondrial membrane potential. Treatment with the SIRT inhibitor nicotinamide increased LDHC acetylation and simultaneously suppressed LDH activity, indicating that hyperacetylation negatively regulates LDHC function. Untargeted metabolomics of LDH-inhibited sperm revealed a notable decrease in guanidinoacetic acid (GAA), the sole precursor of creatine. Supplementing the freezing extender with 600 μM GAA significantly improved post-thaw motility, preserved mitochondrial membrane potential and ATP levels, reduced oxidative stress, and protected acrosome integrity. These improvements were accompanied by elevated intracellular creatine content, enhanced antioxidant capacity (increased T-AOC, CAT, and SOD activities, decreased MDA), and reduced apoptosis. Our findings demonstrate that cryopreservation-induced LDHC hyperacetylation impairs enzyme activity and sperm quality, and that GAA replenishment effectively counteracts this injury through creatine-dependent and antioxidant mechanisms.
Read the paper
Related studies
- Biportal endoscopic versus microscopic lumbar decompressive laminectomy in patients with spinal stenosis: A randomized controlled trial
- A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial
- Supplement-based nutritional strategies to tackle frailty: A multifactorial, double-blind, randomized placebo-controlled trial
- A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression
- Creatine supplementation (3 g/day) and bone health in older women: a 2-year, randomized, placebo-controlled trial
- A Multi-Ingredient Nutritional Supplement in Combination With Resistance Exercise and High-Intensity Interval Training Improves Cognitive Function and Increases N-3 Index in Healthy Older Men: A Randomized Controlled Trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.