New Insights into Ornidazole-Induced Male Reproductive Toxicity in Rats via Energy Metabolism Disruption

Qiujian Feng^1,2Zhuozhi Gong²Xuefan Jiang¹Xiaojing An²Bin Yan²Elena Colonnello³Fu Wang²Jun Guo²Shengjing Liu^2*

• ¹Bejing University of Chinese Medicine, Beijing, China
• ²China Academy of Chinese Medical Sciences Xiyuan Hospital, Beijing, China
• ³Universita degli Studi di Roma Tor Vergata, Rome, Italy

Background: Ornidazole (ORN), as an emerging environmental contaminant, has been shown to exert reproductive toxicity. However, previous studies lacked detailed pathological characterization and mechanistic investigation. Therefore, a re-evaluation of the toxicological effects of ornidazole on the reproductive system is warranted.Methods: Ninety-six male Sprague-Dawley rats were randomly divided into eight groups (n = 12/group), including six ORN-treated groups and two controls. ORN was administered orally at 200, 400, or 800 mg/kg/day for 14 or 28 days. Controls received 1% sodium carboxymethyl cellulose. Body weight, organ indices, sperm concentration and motility were evaluated. Histopathological and ultrastructural changes were assessed using HE staining and scanning electron microscopy. Targeted metabolomic profiling of epididymal and testicular tissues identified differential metabolites.Results: After 14 days or low-dose (200 mg/kg) ORN for 28 days, no significant differences in sperm parameters or tissue histology were observed. However, 400 mg/kg for 28 days induced a significant decline in sperm motility with minimal histological changes, establishing an AS model. At 800 mg/kg, significant reductions in sperm count, motility, and tissue integrity were observed, modeling OAS. Metabolomic analysis revealed ORN disrupted glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathway, indicating energy metabolism impairment as a key pathogenic mechanism.These findings demonstrate the reproductive toxicity of ORN as an emerging environmental contaminant. A dose of 400 mg/kg established a reliable rat model of AS, while 800 mg/kg induced OAS with pronounced histopathological damage. Energy metabolism dysfunction appears to be the central pathogenic mechanism. The current study lays the foundation for further exploration of the effects of antibiotic on testicular toxicology.