Knockdown of the adipokinetic hormone receptor inhibits the reproduction of female Culex pipiens pallens (Diptera: Culicidae) by downregulating L-homoserine and serotonin levels.

The adipokinetic hormone (AKH) receptor, interacting with AKH, regulates the metabolism of amino acids, carbohydrates, and lipids. The AKH receptor is abundant in mosquito primary and secondary sexual organs; however, the exact role of the AKH receptor in mosquito reproductive processes and the specific mechanisms involved are unclear. Among different tissues of adult female mosquitoes (Culex pipiens pallens), the ovaries and fat body showed high expression of the AKH receptor gene. Silencing this gene led to anti-reproductive effects, including abnormal ovarian morphology, reduced follicle number, and a decreased egg-laying count. Meanwhile, decreased yolk accumulation and iron deposition in the ovaries during the vitellogenesis phase were observed, accompanied by reduced expression levels of the vitellogenin-A1 precursor gene and transferrin gene. Liquid chromatography-mass spectrometry analysis revealed a decrease in L-homoserine and serotonin levels following AKH receptor gene knockdown, and supplementation with the above 2 metabolites partly rescued the anti-reproductive phenotype and increased the expression of the vitellogenin-A1 precursor gene and transferrin gene in the AKH receptor gene knockdown mosquitoes. Consistent with the gene knockdown results, Relugolix, an inhibitor of this receptor, likewise affected egg production. Herein, we revealed evidence for the function and potential mechanism of the AKH receptor during female mosquito reproduction, possibly offering an alternative method to control mosquitoes.