Endocrine-metabolic modulators in sperm biotechnology: cross-species mechanisms and translational priorities

Endocrine-metabolic dysregulation is increasingly recognized as a determinant of male reproductive competence. Its implications for sperm biotechnology remain under-integrated. This review advances a systems framework in which insulin resistance (IR), adipokine imbalance, and vitamin D-calcium signaling converge on core sperm functional modules, i.e., membrane lipid architecture, mitochondrial efficiency, redox stability, and capacitation kinetics. Across species, metabolic strain is associated with oxidative vulnerability and altered substrate handling - amplifying damage during cooling, cryopreservation, and sorting. Adipokines emerge as biomarkers of energy-inflammatory state and as functional modulators within seminal plasma and at the sperm surface, with dose- and context-dependent effects on motility and survival. The vitamin D axis, through Ca²⁺-gated signaling, intersects with motility architecture and activation timing, suggesting compatibility constraints during selection and post-thaw use. By mapping endocrine inputs onto specific biotechnology "pinch-points", we propose an endotype-driven model for donor stratification and protocol customization. Stress-response phenotyping, function-rich endpoints beyond conventional motility, and standardized reporting of processing metadata are emphasized to enable cross-study comparability. Stratified trials, process-aware outcome measures, and reverse translation of functional assays between animal and human contexts are translational priorities. Current evidence supports further investigation of donor-stratified metabolic phenotyping as a potential approach to sperm processing, with the aim of reducing sublethal dysfunction and improving predictability of fertility under real-world assisted reproduction workflows. In veterinary reproduction, this framework is especially relevant to artificial insemination-center donor stratification, cryobank intake, chilled-semen transport, and quality control of frozen or sex-sorted semen doses.