Fenvalerate (FEN), a pyrethroid insecticide used worldwide, has been shown to produce a potentially adverse effect on male reproduction. However the mechanisms are not completely understood. Thus this study aimed to (1) determine whether cellular apoptosis was involved in FEN-induced testicular damage in rats, and (2) identify the potential mechanism involved in FEN-induced apoptosis in testes. Data demonstrated that FEN markedly decreased serum testosterone levels, increased the inner diameter of seminiferous tubules, decreased the layers of spermatogenic cells, disturbed spermatogenesis and increased the number of apoptotic cells. Further, bioinformatic analysis of gene microarray in rat testis tissue showed that FEN significantly altered the expressions of genes (Krt8, Mal, Cd24, Lcn2, Phlda1, Arg2) related to apoptotic related processes. The expression pattern of these 6 genes was upregulated in FEN-treated rat testicular tissue. qRT-PCR analysis demonstrated that Phlda1, a well-documented pro-apoptotic factor, was significantly elevated by FEN. The expression of PHLDA1 testicular protein was also elevated following FEN exposure. In conclusion, our results suggest that FEN exposure induced deleterious effects on rat testes associated with Phlda1-mediated apoptosis which may act as a molecular mechanism underlying FEN induced rat testicular damage.

中文翻译：

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Phlda1基因在氰戊菊酯诱导的Sprague-Dawley大鼠凋亡和睾丸损伤中的作用。

Fenvalerate（FEN）是一种在全世界范围内广泛使用的拟除虫菊酯杀虫剂，已被证明会对男性生殖产生潜在的不利影响。但是，机制尚未完全理解。因此，本研究旨在（1）确定细胞凋亡是否参与了FEN诱导的大鼠睾丸损伤，（2）确定了FEN诱导的睾丸细胞凋亡的潜在机制。数据表明，FEN显着降低血清睾丸激素水平，增加生精小管的内径，减少生精细胞的层数，干扰生精能力，并增加凋亡细胞的数量。此外，对大鼠睾丸组织中基因芯片的生物信息学分析表明，FEN显着改变了与凋亡相关过程相关的基因（Krt8，Mal，Cd24，Lcn2，Phlda1，Arg2）的表达。在FEN处理的大鼠睾丸组织中，这6个基因的表达模式上调。qRT-PCR分析表明，FEN可显着提高Phlda1（一个有据可查的促凋亡因子）的水平。FEN暴露后，PHLDA1睾丸蛋白质的表达也升高。总之，我们的结果表明FEN暴露对与Phlda1介导的细胞凋亡相关的大鼠睾丸具有有害作用，这可能是FEN诱导大鼠睾丸损伤的分子机制。