Cannabidiol Inhibited Reproductive Ability of Zebrafish (Danio Rerio) with Gender-Dependent Manner

Abstract Cannabidiol (CBD), a medically active component of hemp, is a popular ingredient in healthcare and personal-care products. The increasing demand for CBD and the legalization of hemp growth may promote chronic exposure of non-target organisms and animals to CBD. In the present study, the reproductive toxicity of CBD was investigated using zebrafish as a model organism. With CBD treatment, parent female zebrafish spawned less with higher natural mortality and malformation rates, showed a decreased gonadosomatic index with an increased percentage of pre-mature oocytes and sperm and had an increased hepatosomatic index. The value of estrogen/testosterone (E2/T) decreased in female zebrafish and increased in male zebrafish. Vitellogenin content was decreased in both female and male zebrafish. Reproductive-related genes were downregulated in the zebrafish brain and liver, whereas esr-α, esr-β, and ar were downregulated in ovaries and upregulated in testicles. Sex hormone synthesis genes were downregulated in ovaries and upregulated in testicles, except for cyp11a, in contrast to the other genes. Apoptosis-related genes were upregulated in the zebrafish brain, gonad, and liver. These results show that CBD might damage the hypothalamus-pituitary-gonad-liver axis function by inducing an apoptotic response, further inhibiting zebrafish reproductive ability in a sex-dependent manner.