Background: Systemic inflammation can disturb testicular immune homeostasis and compromise the blood–testis barrier (BTB), with subsequent impairment of male reproductive function. However, the temporal involvement of the atypical chemokine receptor ACKR5/GPR182 and its ligand CXCL12 in testicular inflammation remains poorly understood.
Objectives: This study investigated temporal changes in the testicular ACKR5/GPR182–CXCL12 axis following lipopolysaccharide (LPS)-induced systemic inflammation in adult male rabbits and examined their associations with inflammatory mediators, BTB-related gene expression, barrier permeability, and sperm quality.
Methods: Adult male albino rabbits were randomly assigned to control and LPS-treated groups and evaluated at 24 h, day 14, and day 56 after a single intraperitoneal injection of LPS (50 μg/kg). Serum and testicular concentrations of TNF-α, IL-1β, IL-6, IL-10, and CXCL12 were determined by ELISA. Testicular expression of GPR182/ACKR5, CXCL12, TJP1/ZO-1, OCLN, and CLDN11 was assessed by RT-qPCR. BTB permeability was evaluated by Evans blue extravasation, while cauda epididymal sperm were assessed for concentration, motility, viability, morphology, and DNA/chromatin integrity.
Results: LPS induced a pronounced early systemic and testicular inflammatory response, accompanied by increased CXCL12 concentrations and altered expression of the ACKR5/GPR182–CXCL12 axis. These changes coincided with increased testicular Evans blue extravasation and reduced expression of the BTB-associated genes TJP1, OCLN, and CLDN11. The greatest disturbances were generally observed during the early phase, followed by progressive recovery at later sampling times. Nevertheless, some molecular and reproductive alterations persisted through day 56. LPS exposure also significantly reduced sperm concentration, motility, and viability and impaired sperm DNA/chromatin integrity, demonstrating a time-dependent reproductive response.
Conclusions: A single systemic LPS challenge induces temporally dynamic inflammatory, chemokine, and BTB-associated alterations in the rabbit testis, accompanied by impaired sperm quality. The coordinated changes in CXCL12 and ACKR5/GPR182 suggest that this atypical chemokine receptor axis may participate in the regulation of the testicular inflammatory microenvironment. Its temporal association with BTB-related gene expression, increased barrier permeability, and sperm impairment identifies the ACKR5/GPR182–CXCL12 axis as a potential link between systemic inflammation and male reproductive dysfunction.