miRNA-GABA influences female Aedes aegypti reproduction by modulating midgut homeostasis

Aedes aegypti's exceptional reproductive capacity drives the global proliferation of vector-borne diseases, including dengue, Zika, and chikungunya, while its hematophagous digestion supplies essential energy to catalyze critical reproductive processes. Our study reveals a significant microRNA (miRNA)-mediated mechanism. We demonstrate that miRNA-7 (miR-7) regulates γ-aminobutyric acid (GABA) levels in the midgut, thereby maintaining intestinal homeostasis. Comprehensive small RNA sequencing identifies miR-7 as a key regulatory molecule sensitive to blood meal digestion kinetics. Mechanistically, miR-7 directly targets glutamate decarboxylase to modulate the glutamate-GABA metabolic balance in the midgut. Concomitantly, female mosquitoes exhibit compromised midgut protease activity, disrupted fat body lipid storage, and diminished fecundity. This study delineates a hierarchical regulatory framework wherein miR-7-GABA modulates the efficiency of blood meal digestion and ultimately governs reproductive fitness.