Browsing by Author "Ahmed, Tahmina Hossain"

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    Molecular action of pyriproxyfen: Role of the Methoprene-tolerant protein in the pyriproxyfen-induced sterilization of adult female mosquitoes
    Ahmed, Tahmina Hossain; Saunders, T. Randolph; Mullins, Donald E.; Rahman, Mohammad Zillur; Zhu, Jinsong (2020-08)
    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 inAedes aegyptimosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fedAe.aegyptifemales 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, includingHR3andE75A, 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 inAe.aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF. Author summary Aedes aegyptimosquitoes are responsible for the transmission of dengue, yellow fever, chikungunya, and Zika fever. Insecticides are widely used as the primary tool in the prevention and control of these infectious diseases. In light of the rapid increase of insecticide resistance in mosquito populations, there is an urgent need to find new classes of insecticides with a different mode of action. Here we found that pyriproxyfen, an analog of insect juvenile hormone (JH), had a large impact on the oocyte development, both before and after blood feeding, in female mosquitoes. Pyriproxyfen disturbed normal hormonal responses and caused metabolic shifting in female adults. These actions appear to collectively impair oocyte development and substantially reduce viable progenies of female mosquitoes. Besides, we demonstrated the involvement of the JH receptor Met in pyriproxyfen-induced female sterilization. This study significantly advances our understanding of mosquito reproductive biology and the molecular basis of pyriproxyfen action, which are invaluable for the development of new mosquito control strategies.
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    Underlying mechanisms of juvenile hormone (JH) and its analog in regulating mosquito reproduction
    Ahmed, Tahmina Hossain (Virginia Tech, 2020-12-07)
    Mosquito reproduction is tightly regulated by the endocrine system. The sesquiterpenoid insect hormone, Juvenile hormone (JH), plays a crucial role in mosquito reproductive maturation. JH signaling pathways consist of a hierarchy of transcriptional regulators that modulate the transcriptional responses to this hormone. Genomic action of JH is mediated through the intracellular receptor Methoprene tolerant (Met) and Krüppel homolog 1 (Kr-h1), an intermediate effector that acts downstream of Met. Kr-h1 is an essential transcription factor for proper oogenesis and egg production in several insects. However, the regulatory mechanism of Kr-h1 in mosquito reproduction has not been well studied. In the current study, we performed global analyses of the Kr-h1 binding sites at multiple time points before and after a blood meal. In addition to known JH-regulated genes, we identified the binding of Kr-h1 to several genes that are controlled by the insect steroid hormone 20-hydroxyecdysone (20E). Kr-h1 seemed to have different roles in regulating the 20E-responsive genes before and after the blood-feeding. RNAi mediated Kr-h1 silencing demonstrated the activator role of Kr-h1 on several 20E-regulated genes in the previtellogenic stage, while Kr-h1 mostly repressed those genes after blood feeding. On the genes that were activated by Kr-h1 in the previtellogenic stage, the binding of Kr-h1 was associated with an increase of the histone marker H3K27ac. For the first time, we demonstrated that the regulatory action of Kr-h1 involves histone modification on the 20E-responsive genes. This study significantly extends our understanding of the regulatory mechanism of Kr-h1, and the cross-talk of JH and 20E in coordinating mosquito reproduction. JH analogs are commonly used as mosquito larvicides. Recent studies reported that the application of a JH analog, pyriproxyfen (PPF), on adult female mosquitoes substantially reduces their reproduction. A big knowledge gap was the poor understanding of the mechanism underlying this sterilizing effect of PPF. Here, with our customized laboratory setup that mimics the bed net intervention, we established a dose-dependent effect of PPF in compromising mosquito fecundity and fertility. We carefully assessed the effects of PPF exposure on mosquito physiology and follicular development. PPF induced excessive growth of primary follicles during the previtellogenic stage. However, the follicular development in the PPF-treated mosquitoes was severely impaired after blood feeding. The primary follicles were much smaller than their counterparts in the control groups and their development stopped at Christopher's stage III. Moreover, PPF triggered the atypical premature growth of secondary follicles at ~36 h PBM. In addition to the follicular developmental reprogramming, PPF also altered the levels of storage metabolites, enhancing the accumulation of glycogen and triglyceride (TAG) before a blood meal and speeding their depletion after blood-feeding. Consistent with the observed phenotypical changes and relevant metabolic genes, several 20E-responsive genes were significantly altered in their expression as a result of PPF exposure. Furthermore, RNAi experiments demonstrated that the JH receptor Met is required in the PPF-induced sterilization. In summary, we evaluated the sterilizing effects of PPF on mosquito reproduction, investigated the molecular action of PPF in regulating mosquito gene expression, and determined the signaling pathway involved in the PPF-induced sterilization of female mosquitoes.