Metabolic remodelling and dynamic integration of ATP supply from spermatogenesis to mature sperm function.

Abstract

Male germ cell development begins with spermatogonial stem cell self-renewal and proceeds through meiosis and spermiogenesis, followed by epididymal maturation to generate mature sperm capable of motility and fertilisation. During this process, ATP demands and the physiological environment of germ cells change progressively. Therefore, ATP supply strategies are shaped by adaptation to stage-specific physiological constraints rather than by selection of pathways with the highest energetic efficiency. In the testes, metabolic pathways are remodelled in a stage-dependent manner in response to requirements for stemness and genome stability, changes in substrate availability associated with passage across the blood-testis barrier, energetic demands of meiosis, and extensive cellular reorganisation during spermiogenesis. Although sperm have limited transcriptional and translational capacities in the epididymis, their membrane properties, signalling systems, and metabolic functions mature through exposure to region-specific luminal environments and molecular transfer from the epididymal epithelium. In mature sperm, glycolysis and oxidative phosphorylation are spatially compartmentalised yet functionally coordinated, with their relative contributions adjusted in response to substrate availability, oxygen tension, and functional demand. Additional processes, including carbon recycling potentially mediated by gluconeogenesis-like reactions, may support ATP homeostasis under specific conditions. This review re-evaluates these findings within a unified framework in which physiological constraints define the metabolic pathways available at each developmental stage, thereby reshaping ATP supply strategies. Metabolic remodelling in the testes, maturation in the epididymis, and integration in mature sperm thus represent successive and interconnected processes that establish adaptive ATP supply throughout male germ cell development.