Fertility decline in female mosquitoes is regulated by the orco olfactory co-receptor

Female Aedes aegypti mosquitoes undergo multiple rounds of reproduction, known as gonotrophic cycles. These cycles span the period from blood meal intake to oviposition. Understanding how reproductive success is maintained across gonotrophic cycles allows for the identification of molecular targets to reduce mosquito population growth. Odorant receptor co-receptor (orco) encodes a conserved insect-specific transmembrane ion channel that complexes with tuning odorant receptors (ORs) to form a functional olfactory receptor. orco expression has been identified in the male and female mosquito germline, but its role is unclear. We report an orco-dependent, maternal effect reduction in fertility after the first gonotrophic cycle. This decline was rescued by repairing the orco mutant locus. Eggs deposited by orco mutant females are fertilized but the embryos reveal developmental defects, reduced hatching, and changes in ion channel signaling gene transcription. We present an unexpected role for an olfactory receptor pathway in mosquito reproduction. HIGHLIGHTSO_LILoss of the orco olfactory co-receptor promotes female mosquito fertility decline. C_LIO_LIAfter their first reproductive cycle completes, Ae. aegypti orco mutant females produce embryos with disrupted development and reduced hatching. C_LIO_LICRISPR/Cas9-mediated repair of the orco mutation rescues the fertility defect. C_LIO_LIGene expression profiling of embryos from orco mutant females supports a role for ion channel signaling in mosquito development. C_LI