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睾酮可恢复氯氰菊酯中毒大鼠恶化的雄性生育能力。

Testosterone recuperates deteriorated male fertility in cypermethrin intoxicated rats.

作者信息

Katragadda Vasudha, Adem Meghapriya, Mohammad Reshma Anjum, Sri Bhasyam Sainath, Battini Kishori

机构信息

Department of Biotechnology, Sri Padmavati Mahila Visvavidyalayam (Women's University), Tirupati, AP 517 502 India.

Department of Biotechnology, Vikrama Simhapuri University, Nellore, AP 524 320 India.

出版信息

Toxicol Res. 2020 Jul 7;37(1):125-134. doi: 10.1007/s43188-020-00046-1. eCollection 2021 Jan.

Abstract

The present study investigates the protective effects of testosterone against reproductive toxicity induced by cypermethrin (50 mg/kg body weight) in rats. Significant reduction in the testicular and accessory sex organ weights were observed in cypermethrin-treated rats over controls. Cypermethrin intoxication significantly reduced testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability and HOS-tail coiled sperm accompanied by significant reduction in the activity levels of testicular steroidogenic enzymes such as 3β- and 17β- hydroxysteroid dehydrogenases in rats as compared to controls. Further, qPCR studies indicated that the mRNA expression levels of steroidogenic acute regulatory protein (StAR) significantly decreased in cypermethrin-treated rats over controls. Molecular docking analysis indicated that the binding affinity of cypermethrin (- 11.2 kcal/mol) towards StAR protein was greater as compared to its natural ligand, cholesterol (- 8.2 kcal/mol) suggesting improper cholesterol channeling across the testis. Significant reduction in the circulatory levels of testosterone was also recorded in cypermethrin-exposed rats. An increase in pre- and post-implantation loss was observed in rats cohabited with cypermethrin-treated rats. On the other hand, testosterone (4.16 mg/kg body weight) treatment ameliorated cypermethrin-induced reprotoxic effects in rats. To conclude, cypermethrin-induced deterioration of suppressed reproductive performance in male rats could be linked to its antiandrogenic effects and on the other hand, testosterone-mediated protection of male reproductive health in cypermethrin-treated rats at least in part occurs via restoration of testosterone biosynthesis, spermatogenesis and sperm maturation events.

摘要

本研究调查了睾酮对氯氰菊酯(50毫克/千克体重)诱导的大鼠生殖毒性的保护作用。与对照组相比,氯氰菊酯处理的大鼠睾丸和附属生殖器官重量显著降低。氯氰菊酯中毒显著降低了大鼠睾丸每日精子计数、附睾精子计数、精子活力、精子存活率和HOS尾部卷曲精子,同时与对照组相比,大鼠睾丸类固醇生成酶如3β-和17β-羟基类固醇脱氢酶的活性水平显著降低。此外,qPCR研究表明,与对照组相比,氯氰菊酯处理的大鼠中类固醇生成急性调节蛋白(StAR)的mRNA表达水平显著降低。分子对接分析表明,氯氰菊酯(-11.2千卡/摩尔)对StAR蛋白的结合亲和力高于其天然配体胆固醇(-8.2千卡/摩尔),表明睾丸中胆固醇转运不当。氯氰菊酯暴露的大鼠循环睾酮水平也显著降低。与氯氰菊酯处理的大鼠同居的大鼠中,着床前和着床后损失增加。另一方面,睾酮(4.16毫克/千克体重)治疗改善了氯氰菊酯诱导的大鼠生殖毒性作用。总之,氯氰菊酯诱导的雄性大鼠生殖性能抑制的恶化可能与其抗雄激素作用有关,另一方面,睾酮介导的对氯氰菊酯处理大鼠雄性生殖健康的保护至少部分是通过恢复睾酮生物合成、精子发生和精子成熟事件实现的。

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