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A preliminary study on the reproductive toxicity of GS-5734 on male mice

Fan, J.; Zhao, D.; Li, X.; Deng, T.; Sun, Y.; Luo, J.; Weng, Y.

2020-04-23 developmental biology
10.1101/2020.04.21.050104 bioRxiv
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BackgroundGS-5734 as a novel and promising medicine for COVID-2019, its biological impact on the mammalian reproductive system has not been systematically studied. The aim of this study was to evaluate the effects of GS-5734 on sperm parameters and spermatogenesis in mice. Materials and MethodsIn this study, GS-5734 was synthesized according to the report. 28 adult male mice were randomly segregated into four groups (n=7 for each group). The group 1 was set as the control group, the group 1, 2, 3 and 4 were administered with GS-5734 at a daily dose of 0, 10, 50, 150 g/mouse respectively, by intraperitoneal injection for 10 days. On the 7th day after the last injection, the testes and cauda epididymides were collected for HE staining and sperm concentration, motility, morphology analysis. ResultsThe results indicated that after treated with GS-5734, the total sperm count and motile sperm rate showed downward trends, the abnormal sperm rate showed an increasing trend. As compared with the control group, GS-5734 at a daily dose of 150 g/mouse caused a significant decrease in sperm concentration and motility, and a significant increased of abnormal sperm rate; the 50 g/mouse drug treatment lead to a significant decrease in sperm motility and an increase in abnormal sperm rate. The HE staining of testicular and epididymal tissues showed that the spermatogenesis of mice was significantly deteriorated with the increasing dosage of GS-5734, especially in the 150 g/mouse group. ConclusionOur findings suggest that a high dosage of GS-5734 may induce testicular toxicity and result in deterioration of sperm parameters in mice. More investigation on the reproductive toxicity of GS-5734 is required.

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