Luteinizing Hormone Plasmid Therapy Results in Long-Lasting High Circulating Lh and Increased Sperm Production in European Sea Bass (Dicentrarchus labrax)

Abstract

The present work aimed at evaluating the potential of intramuscular injection of a hormone-coding gene as an approach for gene therapy in fish. A plasmid containing luteinizing hormone (Lh) in a single-chain (sc) form, pCMV-scLh, was chosen as the coding gene, and sea bass was chosen as the target species. In vivo injection of pCMV-scLh in muscle of juvenile sea bass rendered plasma Lh levels higher than 50 ng/ml in 40% of the injected fish, while these Lh levels were only detected in 4% of controls. Injections performed on spermiating broodstock demonstrated that this strategy produced an active Lh able to increase sperm production without affecting its quality, in terms of density. Compared with the injection of a recombinant single-chain Lh, plasmid injection provoked longer-lasting and higher plasma Lh levels. These results show that sea bass skeletal muscle is able to uptake plasmid DNA and to secrete the encoded protein to the bloodstream. Therefore, we propose somatic gene transfer as a realistic approach for hormone therapy of dysfunctions due to low hormone levels in fish or just to synchronize spawning.