Alterations in Kiss1-Gnrh1 and Testicular Steroidogenic Gene Expression Following α-Terpineol Exposure in Male Rats.

The present study investigated whether repeated oral exposure to α-terpineol is associated with alterations in Kiss1-GnRH-related HPG-axis signaling and testicular steroidogenesis in male Sprague-Dawley rats. Adult male rats received α-T (75, 150, or 300 mg/kg/day) by oral gavage for 28 days. Reproductive hormone levels, sperm characteristics, organ weights, testicular histopathology and ultrastructure, oxidative stress biomarkers, DNA damage, Nrf2 immunoreactivity, and expression of genes involved in HPG-axis regulation and steroidogenesis were evaluated. Repeated α-T exposure associated with dose-dependent reproductive toxicity characterized by significant reductions in reproductive organ weights, circulating GnRH, LH, FSH, and testosterone levels (T), impaired sperm count, motility and viability, increased sperm abnormalities, and marked testicular histopathological and mitochondrial ultrastructural alterations. α-T was associated with oxidative stress, evidenced by increased lipid peroxidation (MDA), depletion of antioxidant defenses (SOD, CAT, GSH), enhanced Nrf2 immunoreactivity, and increased testicular DNA damage. Molecular analyses revealed significant downregulation of Kiss1, Gnrh1, Lhb, Star, Hsd3b, and Cyp11a1, accompanied by enrichment of pathways associated with GnRH signaling, steroidogenesis, and reproductive endocrine regulation. Together, these findings demonstrate male reproductive toxicity following repeated α-terpineol exposure and identify accompanying changes in selected Kiss1-GnRH-associated, steroidogenic, and oxidative-stress endpoints; however, the causal contribution of these pathways remains to be established.