Experimental Evaluation of Sorbitol's Impact on the Testicular Axis in Male Wistar Rats

Infertility is a growing public‑health concern with male factors contributing substantially; sorbitol use as a low‑calorie sweetener raises questions about its reproductive effects. This study evaluated regimen‑ and dose‑dependent impacts of oral sorbitol on the male reproductive axis in adult Wistar rats.

Thirty‑six animals were assigned to control groups or to acute (4 weeks) and chronic (8 weeks) low‑dose (45 mg/kg) and high‑dose (90 mg/kg) sorbitol groups; ethical approval was obtained. Outcomes included body and testicular weight, sperm count, morphology and vitality; serum GnRH, FSH, LH and testosterone; serum and testicular lipid profiles; oxidative markers (MDA, GSH, SOD, GPX); inflammatory markers (TNF‑α, CRP); and histology (H&E, Masson trichrome).

Body weight was unchanged across groups, while chronic high‑dose sorbitol caused significant testicular weight reduction. Acute low‑dose exposure increased sperm count but also raised abnormal forms and altered viability, whereas chronic regimens reduced sperm counts. Hormonal responses were regimen specific: acute high dose transiently elevated testosterone and acute low dose increased LH, but chronic high dose produced marked GnRH suppression with downstream gonadotropin decline. Lipid profiling revealed acute systemic lipid shifts and chronic intratesticular lipid accumulation, paralleling compartmentalised changes in oxidative stress. Acute exposure reduced some systemic oxidative markers and increased testicular GSH, but chronic high dose increased testicular MDA and induced GPX, with reconfigured TNF‑α/CRP signalling. Histology showed early seminiferous epithelial disruption in acute groups and interstitial collagen deposition consistent with evolving fibrosis in chronic groups.

These mixed biochemical, hormonal and structural findings indicate potential short‑term metabolic signals yet clear long‑term reproductive risks from chronic high‑dose sorbitol, warranting longitudinal mechanistic and interventional studies.