Manipulation of metabolism to improve liquid preservation of mammalian spermatozoa

Reproductive success in mammals hinges on the ability of sperm to generate sufficient energy through cellular metabolism to perform the energy-intensive processes required for fertilisation, including motility, maturation, and oocyte interactions. It is now widely accepted that sperm exhibit metabolic flexibility, utilising a combination of glycolysis and oxidative phosphorylation (supported by the Krebs cycle and other complementary pathways) to meet their energy demands. However, the preferred pathway for energy production varies significantly among species, making it challenging to map species-specific metabolic strategies, particularly in species with high metabolic flexibility, like the ram. Additionally, differences in methodologies used to measure metabolism have led to biased interpretations of species’ metabolic strategies, complicating the development of liquid storage methods aimed at preserving spermatozoa by manipulating energy generation based on species-specific requirements. This review examines sperm energy requirements, current methods for assessing metabolic capacity, and the current research on species-specific metabolism. Future research should focus on establishing a standardised approach for determining metabolic preferences to accurately map species-specific strategies, a critical step before developing effective liquid preservation methods. By identifying species-specific regulatory points, strategies can be designed to temporarily inhibit metabolic pathways, conserving resources and reducing the accumulation of metabolic by-products. Alternatively, supplementation with depleted metabolites can be guided by understanding areas of excessive consumption during prolonged metabolism. Applying this knowledge to develop tailored preservation techniques will help minimise sperm damage and improve survival during in vitro processing and liquid storage, ultimately enhancing the success of artificial breeding programs.