dc.contributor.author	Ahmed, Tahmina Hossain	en
dc.contributor.committeechair	Zhu, Jinsong	en
dc.contributor.committeemember	Gillaspy, Glenda E.	en
dc.contributor.committeemember	Lahondère, Chloé	en
dc.contributor.committeemember	Tu, Zhijian	en
dc.contributor.department	Biochemistry	en
dc.date.accessioned	2022-06-01T06:00:16Z	en
dc.date.available	2022-06-01T06:00:16Z	en
dc.date.issued	2020-12-07	en
dc.description.abstract	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.	en
dc.description.abstractgeneral	Among different insect-borne diseases, mosquito causes the highest disease burden with almost 700 million infections and over a million deaths every year. Aedes aegypti mosquitoes are the major vehicle to transmit several viral diseases including dengue, yellow fever, chikungunya, and Zika fever. They pose a global threat to public health and economic sectors. Different mosquito control strategies are used, and a very quick, powerful, and popular strategy is using chemical insecticides to decrease mosquito populations. However, insecticide resistance in mosquitoes and non-specific toxicity to other animals are great challenges associated with the commonly used insecticides. To resolve this problem, new insecticides are urgently needed. If we can broaden our understanding of mosquito reproductive biology, new targets will be identified and can be exploited to develop new insecticides. In our study, we investigated an insect-specific hormone, Juvenile hormone (JH), to understand its regulatory action in mosquito reproduction. Also, this study improved our knowledge of the molecular understanding of the insecticide (synthetic JH-like compound) in decreasing mosquito egg numbers and reducing the hatching rate. Overall, we gained a significant understanding of the hormonal regulation of mosquito reproduction. This knowledge can be used in the future to develop new insecticides with better efficiency to decrease the mosquito population and mosquito-borne disease burden.	en
dc.description.degree	Doctor of Philosophy	en
dc.format.medium	ETD	en
dc.identifier.other	vt_gsexam:28425	en
dc.identifier.uri	http://hdl.handle.net/10919/110370	en
dc.publisher	Virginia Tech	en
dc.rights	In Copyright	en
dc.rights.uri	http://rightsstatements.org/vocab/InC/1.0/	en
dc.subject	Mosquito	en
dc.subject	Aedes aegypti	en
dc.subject	Juvenile hormone	en
dc.subject	Pyriproxyfen	en
dc.subject	reproduction	en
dc.subject	Oogenesis	en
dc.subject	gene regulation	en
dc.title	Underlying mechanisms of juvenile hormone (JH) and its analog in regulating mosquito reproduction	en
dc.type	Dissertation	en
thesis.degree.discipline	Biochemistry	en
thesis.degree.grantor	Virginia Polytechnic Institute and State University	en
thesis.degree.level	doctoral	en
thesis.degree.name	Doctor of Philosophy	en

Underlying mechanisms of juvenile hormone (JH) and its analog in regulating mosquito reproduction

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