Immune–endocrine interactions in bovine testicular homeostasis: A conceptual framework for reproductive resilience

Bull fertility depends on coordinated regulation of spermatogenesis, endocrine function, immune tolerance, and tissue stress responses. This narrative review synthesizes direct bovine evidence with comparative mammalian mechanisms to evaluate a conceptual framework of coordinated immune–endocrine regulation in testicular homeostasis. At baseline, luteinizing hormone-dependent Leydig-cell steroidogenesis, follicle-stimulating hormone- and androgen-responsive Sertoli-cell functions, resident immune cells, cytokines, redox pathways, and the blood–testis barrier collectively support germ-cell development while limiting damaging immunity. Direct studies in cattle show that this balance is stress sensitive. In Nelore bulls, 48 h of scrotal insulation increased intratesticular temperature from 35.28 to 38.62°C, reduced tissue testosterone from 3,119 to 295.5 ng/g, and markedly suppressed STAR while inducing GPX1 and HSP70. Bovine Sertoli-cell experiments identify TLR4–NF-κB signaling as a causal link between danger sensing, inflammation, mitochondrial injury, and barrier-protein loss. Acute bovine besnoitiosis further demonstrates how vascular injury, inflammatory infiltration, impaired thermoregulation, and germ-cell degeneration can converge in vivo. Recent single-cell and spatial transcriptomic studies now resolve macrophage, T-cell, Leydig-cell, Sertoli-cell, and germ-cell populations in bovine testes, although they do not yet establish causal immune–endocrine communication. Three operational states – homeostatic tolerance, compensated stress, and decompensated inflammation – are used to describe regions of a continuous response spectrum rather than validated, discrete physiological categories. Within this framework, bull subfertility may partly reflect a reduced capacity to maintain coordinated testicular homeostasis. Longitudinal assessment of immune, endocrine, metabolic, and spatial parameters is therefore a priority for further mechanistic validation.