Exposure of adult mosquitoes to pyriproxyfen (PPF), an analog of insect juvenile hormone (JH), has shown promise to effectively sterilize female mosquitoes. However, the underlying mechanisms of the PPF-induced decrease in mosquito fecundity are largely unknown. We performed a comprehensive study to dissect the mode of PPF action in Aedes aegypti mosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fed Ae. aegypti females but blocked the development of primary follicles at Christopher′s Stage III after blood feeding. Secondary follicles were precociously activated in PPF-treated mosquitoes. Moreover, PPF substantially altered the expression of many genes that are essential for mosquito physiology and oocyte development in the fat body and ovary. In particular, many metabolic genes were differentially expressed in response to PPF treatment, thereby affecting the mobilization and utilization of energy reserves. Furthermore, PPF treatment on the previtellogenic female adults considerably modified mosquito responses to JH and 20-hydroxyecdysone (20E), two major hormones that govern mosquito reproduction. Kruppel homolog 1, a JH-inducible transcriptional regulator, showed consistently elevated expression after PPF exposure. Conversely, PPF upregulated the expression of several key players of the 20E regulatory cascades, including HR3 and E75A, in the previtellogenic stage. After blood-feeding, the expression of these 20E response genes was significantly weaker in PPF-treated mosquitoes than the solvent-treated control groups. RNAi-mediated knockdown of the Methoprene-tolerant (Met) protein, the JH receptor, partially rescued the impaired follicular development after PPF exposure and substantially increased the hatching of the eggs produced by PPF-treated female mosquitoes. Thus, the results suggested that PPF relied on Met to exert its sterilizing effects on female mosquitoes. In summary, this study finds that PPF exposure disturbs normal hormonal responses and metabolism in Ae. aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF.

中文翻译：

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少年激素受体甲氧戊丁耐受剂是吡吡氧芬对成年埃及伊蚊的杀菌作用

成年蚊子暴露于吡虫啉（PPF）（一种类似于昆虫幼体激素（JH）的类似物），已显示出对有效灭绝雌性蚊子的希望。但是，PPF诱导蚊子繁殖力下降的潜在机制在很大程度上尚不清楚。我们进行了一项全面的研究，以剖析埃及伊蚊中PPF的作用方式。暴露于PPF会促使含糖Ae的初级卵泡过度生长。埃及雌性动物，但在采血后，在克里斯托弗三期时阻断了初级卵泡的发育。在PPF处理的蚊子中，次级卵泡被早熟激活。而且，PPF实质上改变了许多基因的表达，而这些基因对于脂肪体和卵巢的蚊子生理和卵母细胞发育至关重要。尤其是，PPF处理后，许多代谢基因被差异表达，从而影响能量储备的动员和利用。此外，对产前成卵性成年雌性的PPF处理大大改变了蚊对JH和20-羟基蜕皮激素（20E）的反应，这是控制蚊子繁殖的两种主要激素。Kruppel同系物1（JH诱导的转录调节因子）在PPF暴露后显示出持续升高的表达。相反，PPF在前玻璃体形成阶段上调了20E调控级联反应的几个关键参与者的表达，包括HR3和E75A。采血后，PPF处理的蚊子中这些20E反应基因的表达明显弱于溶剂处理的对照组。RNAi介导的甲氧戊二烯耐受（Met）蛋白，JH受体，PPF暴露后部分挽救了受损的卵泡发育，并大大增加了用PPF处理的雌性蚊子产卵的孵化率。因此，结果表明PPF依赖于Met对雌性蚊子发挥杀菌作用。总而言之，这项研究发现PPF暴露会干扰Ae的正常激素反应和新陈代谢。埃及，在PPF激活的分子靶标和下游信号传导途径上发光。这项研究发现，PPF暴露会干扰Ae的正常激素反应和新陈代谢。埃及，将光照射到分子靶标和由PPF激活的下游信号通路上。这项研究发现，PPF暴露会干扰Ae的正常激素反应和新陈代谢。埃及，在PPF激活的分子靶标和下游信号传导途径上发光。