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 to CBD. In this study, the reproductive toxicity of CBD was investigated on adult zebrafish. With CBD treatment, female zebrafish spawned less with higher natural mortality and malformation rates. Both female and male zebrafish showed a decreased gonadosomatic index with an increased percentage of pre-mature oocytes and sperm and had an increased hepatosomatic index with decreased content of vitellogenin. The value of estrogen/testosterone (E2/T) decreased in female zebrafish and increased in male zebrafish. 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 reproductive function by inducing an apoptotic response, further inhibiting zebrafish reproductive ability.
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Data availability
Data used in this study are included in this article and available on reasonable request from the corresponding author.
Abbreviations
- CBD:
-
Cannabidiol; intake
- E2:
-
Estrogen
- T:
-
Testosterone
- HPGL axis:
-
Hypothalamus-pituitary-gonad-liver axis
- THC:
-
Tetrahydrocannabinol
- CBN:
-
Cannabinoid
- OR:
-
Odd ratio
- DMSO:
-
Dimethylsulfoxide
- Vtg:
-
Vitellogenin
- GSI:
-
Gonadosomatic index
- HIS:
-
Hepatosomatic index
- LOD:
-
Limit of detection
- LOQ:
-
Limit of quantity
- LC50:
-
Median lethal concentration
- GnRH:
-
Gonadotropin-releasing hormone
- LH:
-
Luteinizing hormone
- FSH:
-
Follicle-stimulating hormone
- HPGL axis:
-
Hypothalamus-pituitary-gonad-liver axis
- ROS:
-
Reactive oxygen species
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Acknowledgements
We would like to thank Prof. Demetrio Raldua Perez from the Institute for Environmental Assessment and Water Research (IDAEA-CSIC) for his advice during manuscript writing. We would like to thank Editage (www.editage.cn) for English language editing.
Funding
This study was supported by the National Key Research and Development Program of China [grant number 2019YFC1604504], National Natural Science Foundation of China [grant number 31872006], and Beijing Nova Program of Science and Technology [grant number Z191100001119121].
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Lin Li: Methodology, Formal analysis, Writing-original draft. Bei Fan: Conceptualization. Zhiqiang Kong: Formal analysis, Writing—review & editing. Yifan Zhang: Methodology. MengYing Zhao: Methodology. Jesus Simal-Gandara: Formal analysis. Fengzhong Wang: Funding acquisition, Supervision. Minmin Li: Project administration, Conceptualization.
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All experiments using zebrafish were performed according to the animal protocol and authorized by the laboratory animal welfare and ethics committee of Chinese Academy of Agricultural Sciences (306–05-2006–025, published by Ministry of Science and Technology of the People’s republic of China).
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Li, L., Fan, B., Kong, Z. et al. Short-term exposure of Cannabidiol on Zebrafish (Danio Rerio): Reproductive Toxicity. Environ Sci Pollut Res 30, 75668–75680 (2023). https://doi.org/10.1007/s11356-023-27792-7
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DOI: https://doi.org/10.1007/s11356-023-27792-7