An ovary-enriched piRNA controls ovarian development via Gadd45a-JNK-mediated nurse-cell apoptosis in the arbovirus vector Aedes albopictus.

The Asian tiger mosquito (Aedes albopictus) is a rapidly expanding invasive species and a global vector of arboviruses. Its transmission depends on the female's blood meal-driven reproductive cycle. Although mosquito PIWI-interacting RNAs (piRNAs) research has predominantly focused on antiviral immunity, their roles in reproduction remain poorly understood. Here we profiled sex-biased piRNA expression in Ae. albopictus and identified a female-enriched piRNA, AalpiRNA-18529. This piRNA accumulates in pre-vitellogenic ovaries and is rapidly downregulated after a blood meal. Gain-of-function experiments showed that AalpiRNA-18529 mimics impair follicle development, reduces fecundity and egg hatching, and disrupts nurse-cell apoptosis required for oocyte maturation. Mechanistically, AalpiRNA-18529 represses Gadd45a, a conserved stress-response regulator. Gadd45a knockdown phenocopies AalpiRNA-18529 gain-of-function, leading to reduced phosphorylation of c-Jun N-terminal kinase (JNK) and thus indicating defective activation of the Gadd45a-JNK apoptotic axis. Collectively, our findings reveal a piRNA-mediated pathway that controls ovarian development in Ae. albopictus during vitellogenesis and highlight the AalpiRNA-18529-Gadd45a-JNK cascade as a potential molecular target for genetic strategies to disrupt mosquito reproduction.