METHODS: In this study, we refer to the clinical adult dosage and mode of L-carnitine administration, and after converting to mouse doses, mice were daily intragastrical administered L-carnitine to investigate whether it was harmful to the testis. The investigation involved assessing its potential testicular toxicity through histopathological staining, sperm motility analysis, and quantitative real-time PCR.
RESULTS: Our results showed that L-carnitine increased sperm motility after 14 days of continuous administration, but increased luminal exfoliated spermatogenic cells occurred in the testis, and TUNEL results showed increased apoptotic cells. Compared with the control group, the mRNA expression of the spermatogenic cell marker at each stage was decreased in mice treated for 14 consecutive days of L-carnitine. After 50 days of continuous administration followed by 14 days of drug withdrawal, the total sperm motility of mice was almost 0, and a large number of abnormal eosinophilic spermatogenic cells appeared in the testis. These indicate that oral L-carnitine for more than 14 days impairs spermatogenesis in mice, and sudden discontinuation of administration results in substantial death of established spermatogenic cell populations.
CONCLUSIONS: Our findings suggest that chronic oral administration of L-carnitine impairs spermatogenic function in the testis. The oral administration of L-carnitine to enhance sperm motility should not exceed the 2/5 point of the spermatogenic cycle.
方法:在本研究中,我们指的是左旋肉碱的临床成人剂量和给药方式,转换为小鼠剂量后,小鼠每天胃内给药L-肉碱,以研究其是否对睾丸有害。调查涉及通过组织病理学染色评估其潜在的睾丸毒性,精子运动分析,和定量实时PCR。
结果:我们的结果表明,连续给药14天后,左旋肉碱可增加精子活力,但是睾丸中出现了腔内脱落的生精细胞增加,TUNEL结果显示凋亡细胞增多。与对照组相比,在连续14天接受L-肉碱治疗的小鼠中,每个阶段生精细胞标志物的mRNA表达均降低。连续给药50天后停药14天,小鼠精子总活动力几乎为0,睾丸中出现大量异常嗜酸性生精细胞。这些表明,口服L-肉碱超过14天损害小鼠的精子发生,突然停止给药导致已建立的生精细胞群大量死亡。
结论:我们的研究结果表明,长期口服左旋肉碱会损害睾丸的生精功能。口服L-肉碱以增强精子活力不应超过生精周期的2/5点。