The exposure to nandrolone changed the expression of genes associated with sexual differentiation and disrupted the levels of hormones in the hypothalamic-pituitary-gonadal (HPG) axis, ultimately inducing male differentiation in zebrafish (Danio rerio)

Various anabolic androgenic steroids (AAS) are frequently detected in aquatic environments, yet the potential ecotoxicological impacts of their increased load have not received adequate attention. This study investigates the effects of exposure to the androgen nandrolone on sex differentiation, gonadal development, and the expression of hormones, enzymes, and proteins related to the hypothalamic-pituitary-gonadal (HPG) axis in zebrafish. The results indicate that exposure to nandrolone at 60 days post-fertilization promotes the maturation of spermatogonia, inhibits the development of oocytes, and induces their apoptosis. Additionally, there were dose-dependent changes in male differentiation and hormone levels within the HPG axis: in the high-dose group (5 μg/L), males constituted 73 % of the population, and levels of E2 hormones in gonadal tissues decreased by 33 %, while T hormone levels increased by 55 %. Furthermore, the expression of genes essential for ovarian differentiation were downregulated, whereas the expression of testicular differentiation-related genes were upregulated. The molecular docking results show that the drug can form hydrogen bonds with key proteins, which have high affinity, and are more likely to cause conformational changes in the proteins, thereby altering their activity. KEGG analysis suggests that the MAPK signaling pathway is likely the target pathway through which nandrolone exposure induces reproductive toxicity.