Temporal changes in amino acid profiles coordinate mosquito physiology and egg maturation in Aedes aegypti

Female Aedes aegypti mosquitoes utilize host blood to support egg maturation by digesting, absorbing, and metabolizing its components. Among these, amino acids are essential as both signaling molecules and building blocks for yolk proteins. While their overall importance is established, the individual dynamics and regulation of each amino acid remain insufficiently understood.

We systematically profiled free and protein-bound amino acids in whole bodies, ovaries, and excreta over time after blood feeding, revealing distinct temporal dynamics across amino acids. Notably, tyrosine, enriched in yolk proteins, exhibited a biphasic pattern: a transient decrease between 6 and 9 h post blood meal, followed by accumulation during egg maturation. We also performed RNA-seq and found that amino acid metabolism is partially regulated by 20-hydroxyecdysone (20E), indicating hormonal control of amino acid homeostasis. Integrating RNA-seq analysis with amino acid profiling further suggested an adaptation to metabolic imbalance between host blood and ovaries. The early decrease in tyrosine was attributed to enzymatic degradation by 4-hydroxyphenylpyruvate dioxygenase (Hpd), whose expression is induced by 20E, a key hormone orchestrating post-blood-feeding gene expression and egg maturation. Pharmacological inhibition of Hpd caused tyrosine accumulation and increased lethality, indicating that tight regulation of tyrosine catabolism is essential for survival.

This study highlights the temporally coordinated metabolism of individual amino acids during mosquito reproduction. Our dataset serves as a valuable resource for understanding nutrient allocation with endocrine regulation, as well as a foundation for developing novel strategies to disrupt mosquito survival by targeting the metabolic enzymes.