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We have developed an immersion-based method in fish to eliminate primordial germ cells (PGCs) by silencing a PGC-development-responsible gene, which resulted in the production of reproductively sterile fish. This proposal aims to transfer this fish sterilization technology to produce sterile diploid eastern oysters to avoid triploids mortality issues. The production of sterile diploid oysters without ploidy manipulation could retain the market advantage of sterile oysters and minimize performance compromise. We have identified several candidate genes in eastern oysters that are potentially indispensable for oyster PGC development. Our preliminary experiments by targeting one of the candidate genes, germ-cell-less (gcl), have yielded oysters that are in their third year. The qPCR results reveal a reduced expression of germ cell marker genes after treatment. Histological examination will be used to evaluate gametogenesis of treated oysters upon sexual maturity in their third summer. The growth and survival of treated oysters, diploid controls, and triploid oysters will also be compared. The immersion protocols in oysters will be optimized, and additional two candidate genes will be targeted for disrupting PGC development and achieve sterility induction in oysters. The expected outcomes from this research will promote cost-effective and sustainable oyster aquaculture.