Laboratory of Developmental Biology, Federal University of Sao Paulo, Sao Paulo, Brazil.
J Histochem Cytochem. 2020 May;68(5):327-342. doi: 10.1369/0022155420916274. Epub 2020 Mar 31.
The aim of this study was to investigate carnitine action against negative effects of etoposide on stem/progenitor spermatogonia and on sperm production. Carnitine (250 mg/kg body weight/day) and etoposide (5 mg/kg body weight/day) were administered from 25-days postpartum to 32-days postpartum. Testes were collected at 32-days postpartum, 64-days postpartum, and 127-days postpartum, and submitted to the immuno-labeling of UTF1, SOX2, and PLZF proteins to identify undifferentiated spermatogonia populations. At 127-days postpartum, sperm were collected for analysis. Carnitine+etoposide group showed a higher numerical density of spermatogonia labeled for all studied proteins at 64-days postpartum (critical age) compared to the etoposide group. Moreover, there was an improvement of spermatic parameters and sperm DNA integrity in rats of the carnitine+etoposide group in comparison with rats of the etoposide group. The results suggest that carnitine improves the self-renewal of undifferentiated spermatogonia and promotes a partial protection on them, alleviating the etoposide harmful late effects and leading to an enhancement of the sperm parameters in adulthood.
本研究旨在探讨肉碱对抗依托泊苷对精原干细胞/祖细胞和精子发生的负面影响的作用。肉碱(250mg/kg 体重/天)和依托泊苷(5mg/kg 体重/天)从产后 25 天至产后 32 天给药。在产后 32 天、64 天和 127 天收集睾丸,并进行 UTF1、SOX2 和 PLZF 蛋白的免疫标记,以鉴定未分化的精原细胞群体。在产后 127 天收集精子进行分析。与依托泊苷组相比,肉碱+依托泊苷组在 64 天(关键年龄)时标记所有研究蛋白的精原细胞数量密度更高。此外,与依托泊苷组相比,肉碱+依托泊苷组大鼠的精子参数和精子 DNA 完整性得到改善。结果表明,肉碱可提高未分化精原细胞的自我更新能力,并对其产生部分保护作用,减轻依托泊苷的晚期有害作用,从而提高成年大鼠的精子参数。