Fenvalerate (Fen) is an endocrine disruptor, capable of interfering with the activity of estrogen and androgen. Our objective was to explore the molecular mechanisms of Fen on sperm in vivo. Adult male Sprague–Dawley rats were orally exposed to 0, 0.00625, 0.125, 2.5, 30 mg/kg/day Fen for 8 weeks. Sperm morphology, differential proteomics of sperm and testes, bioinformatic analysis, western blotting (WB), and RT‐PCR were used to explore the mechanism of Fen on sperm. Data showed that low Fen doses significantly induced sperm malformations. In sperm proteomics, 47 differentially expressed (DE) proteins were enriched in biological processes (BPs) related to energy metabolism, response to estrogen, spermatogenesis; and enriched in cellular components (CCs) relating to energy‐metabolism, sperm fibrous sheath and their outer dense fibers. In testicular proteomics, 56 DE proteins were highly associated with mRNA splicing, energy metabolism; and enriched in CCs relating to vesicles, myelin sheath, microtubules, mitochondria. WB showed that the expression of selected proteins was identical to their tendency in 2D gels. Literature indicates that key DE proteins in proteomic profiles (such as Trap1, Hnrnpa2b1, Hnrnpk, Hspa8, and Gapdh) are involved in P53‐related processes or morphogenesis or spermatogenesis. Also, P53 mRNA and protein levels were significantly increased by Fen; bioinformatic re‐analysis showed that 88.5% DE proteins and P53 formed a complex interacting network, and the key DE proteins were coenriched with P53‐related BPs. Results indicate that key DE proteins of proteome underlying sperm malformations of rats exposed to low Fen doses are highly related to P53.

中文翻译：

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暴露于低氰戊菊酯剂量下大鼠精子畸形蛋白质组的关键蛋白与P53高度相关

Fenvalerate（Fen）是一种内分泌干扰物，能够干扰雌激素和雄激素的活性。我们的目标是探索芬对体内精子的分子机制。成年雄性Sprague–Dawley大鼠经口服0，0.00625，0.125，2.5，30 mg / kg /天Fen暴露8周。精子形态，精子和睾丸的差异蛋白质组学，生物信息学分析，蛋白质印迹法（WB）和RT-PCR被用来研究Fen对精子的作用机理。数据显示，低剂量的芬可明显引起精子畸形。在精子蛋白质组学中，47种差异表达（DE）蛋白富集于与能量代谢，对雌激素的反应，精子发生有关的生物过程（BP）。并且富含与能量代谢，精子纤维鞘及其外部致密纤维有关的细胞成分（CC）。在睾丸蛋白质组学中，有56种DE蛋白与mRNA剪接，能量代谢高度相关。并富含与囊泡，髓鞘，微管，线粒体有关的CC。WB显示所选蛋白质的表达与其在2D凝胶中的趋势相同。文献表明，蛋白质组学特征中的关键DE蛋白（例如Trap1，Hnrnpa2b1，Hnrnpk，Hspa8和Gapdh）与P53相关的过程或形态发生或精子发生有关。此外，Fen显着增加了P53 mRNA和蛋白水平；生物信息学重新分析表明，88.5％的DE蛋白和P53形成了一个复杂的相互作用网络，并且主要的DE蛋白与P53相关的BP共富集。结果表明，暴露于低Fen剂量的大鼠精子畸形蛋白质组的关键DE蛋白与P53高度相关。