Aspirin inhibition of prostaglandin synthesis impairs egg development across mosquito taxa

Several endocrine signals are known to mediate mosquito egg development including insulin-like peptide, 20-hydroxyecdysone, and juvenile hormone. The objective of this study was to determine the effects of prostaglandin E2 (PGE2) as an additional mediator of oogenesis in the mosquitoes, Aedes albopictus and Anopheles gambiae. The injection of aspirin (an inhibitor of cyclooxygenase) shortly after blood-feeding significantly inhibited egg development at choriogenesis in a dose-dependent manner in Ae. albopictus. Moreover, oral administration of aspirin to An. albopictus and An. gambiae also inhibited egg production. The aspirin treatment suppressed expression of the genes (Yellow-g and Yellow-g2) associated with exochorion darkening and led to the production of a malformed egg shell in Ae. albopictus. These inhibitory effects of aspirin on egg development were rescued by the addition of PGE2, confirming the specificity of aspirin in inhibiting prostaglandin production. To validate these results, we identified a putative PGE2 receptor (Aa-PGE2R) in Ae. albopictus. Aa-PGE2R expression was highly inducible in adult ovary after blood-feeding. RNA interference of Aa-PGE2R expression resulted in the significant suppression of choriogenesis similar to aspirin treatment, where the addition of PGE2 to Aa-PGE2R-silenced females failed to rescue egg production. Together, these results suggest that PG synthesis and signaling are required for egg development across diverse mosquito taxa. Author SummaryProgstaglandins (PGs) play crucial roles in mediating various physiological processes in insects. Aspirin (ASP) inhibits PG biosynthesis and has been used as an anti-inflammatory drug. ASP injection or feeding to mosquitoes of Aedes albopictus or Anopheles gambiae significantly inhibits egg production at chorion formation. This led to significant reduction in fecundity and egg hatchability. PG signal is interrupted by RNA interference (RNAi) of PGE2 receptor. The RNAi treatment also gave a similar damage to females in egg production as seen in ASP treatment. Thus, PG signal is required for egg production of these mosquitoes. Data Availability StatementAll relevant data are within the manuscript and its Supporting Information file.