Ran Lingxiang, Zhao Rui, Hu Guangmo, Dai Guangcheng, Yao Qiu, Chen Cai, Liu Xiaolong, Xue Boxin
Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Department of Acupuncture and Moxibustion, Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Nanjing, 210006, Jiangsu, China.
Int Urol Nephrol. 2025 Jan;57(1):35-47. doi: 10.1007/s11255-024-04164-9. Epub 2024 Jul 24.
While L-carnitine is commonly used to treat oligoasthenozoospermia, concerns have been raised regarding its potential harm to spermatogenesis. This study aims to investigate the potential testicular toxicity of long-term oral administration of L-carnitine.
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.
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.
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.
左旋肉碱常用于治疗少弱精子症，但人们对其对精子发生的潜在危害表示担忧。本研究旨在探讨长期口服左旋肉碱的潜在睾丸毒性。
在本研究中，我们参考左旋肉碱的临床成人给药剂量和方式，换算成小鼠剂量后，每日给小鼠灌胃左旋肉碱，以研究其是否对睾丸有害。该研究通过组织病理学染色、精子活力分析和定量实时PCR评估其潜在的睾丸毒性。
我们的结果显示，连续给药14天后，左旋肉碱可提高精子活力，但睾丸中管腔内脱落的生精细胞增多，TUNEL结果显示凋亡细胞增多。与对照组相比，连续14天给予左旋肉碱治疗的小鼠各阶段生精细胞标志物的mRNA表达均降低。连续给药50天，停药14天后，小鼠精子总活力几乎为0，睾丸中出现大量异常嗜酸性生精细胞。这些表明口服左旋肉碱超过14天会损害小鼠的精子发生，突然停药会导致已建立的生精细胞群体大量死亡。
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。口服左旋肉碱提高精子活力不应超过生精周期的2/5点。
