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肉碱可减轻青春期前给药成年大鼠中依托泊苷对精原细胞自我更新和精子生成的毒性作用。

Carnitine Diminishes Etoposide Toxic Action on Spermatogonial Self-renewal and Sperm Production in Adult Rats Treated in the Prepubertal Phase.

机构信息

Laboratory of Developmental Biology, Federal University of Sao Paulo, Sao Paulo, Brazil.

出版信息

J Histochem Cytochem. 2020 May;68(5):327-342. doi: 10.1369/0022155420916274. Epub 2020 Mar 31.

Abstract

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.

摘要

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。

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