Endocrine disruptive toxicity of cypermethrin in Labeo catla: Involvement of genes and proteins related to the HPG axis

Cypermethrin (CYP) is a synthetic pyrethroid abundantly used in agriculture and aquaculture. It is an established potent endocrine disruptor to fish, yet the molecular mechanism behind its reproductive toxicity remains unclear. In this study, fish Labeo catla (Catla) was exposed to environmentally relevant concentration of CYP (0.7 μg/L) and 0.14 μg/L for 30 days. The changes in circulating sex steroids, genes, and hormones linked to the hypothalamus-pituitary gonadal (HPG) axis, stress response and associated histological alterations were studied. Significant decline (P < 0.05) in serum 17 beta (β) estradiol (E2), 11 ketotestosterone (11-KT), and brain (FSH and GnRH) were observed in 0.7 μg/L dose of CYP. These effects may be due to the down-regulated expression of the upstream genes of the HPG axis i.e. Kiss 1 and Kiss 2, which further downregulates the expression of the GnRH gene. The decreased level of E2 and 11-KT also affects the vitellogenin (Vtg) gene expression, reducing the production of Vtg, a crucial protein for ovarian development. Principal component analysis (PCA) revealed the relationship between CYP and the biosynthesis of sex steroids. The toxic effect of CYP was also visible in antioxidant enzyme assay and related histological alterations. Overall, the study elucidated that long-term exposure to CYP, even at an environmentally relevant dose, may affect reproductive potential and fish recruitment. The study provides important insights into molecular mechanisms underlying CYP-induced endocrine disruption in fish, and it also raises questions about CYP's potential toxicity at environmentally relevant concentration in terms of understanding ecological risk.