Chronic cylindrospermopsin exposure impairs oocyte growth and maturation by stress-induced endocrine disruption and immune activation of NF-κB/TNF-α pathway in female zebrafish.

Cyanotoxins are one of the major threats to aquatic ecosystems due to their diverse toxic effects on aquatic organisms. Cylindrospermopsin is a globally reported freshwater cyanotoxin that exhibits hepatotoxic, cytotoxic, immunotoxic, and neurotoxic effects in teleosts; however, its harmful effects on reproductive health remain less explored. This study investigates the impacts of cylindrospermopsin on the reproductive endocrine and paracrine system, emphasising the HPGL axis of female zebrafish. Following 14 days of in-vivo cylindrospermopsin exposure, decreased gonadosomatic and hepatosomatic indices were observed. The number of fully grown (vitellogenic and post-vitellogenic) oocytes was decreased in treated groups, signifying oocyte growth impairments. Disruption of serum gonadotropin levels (FSH and LH) and steroid (17β-estradiol/testosterone) ratio was also observed, indicating the endocrine-disrupting effects of cylindrospermopsin. Following in-vitro cylindrospermopsin exposure for 8 h, increased GVBD was observed, representing early oocyte maturation. Besides endocrine regulation, stress-induced immune-activation of paracrine factors also regulates oocyte maturation. Subsequently, elevated lipid peroxidation and antioxidant activity were observed in the ovary of exposed groups, which disrupts the expression of different steroidogenesis and antioxidant marker genes. This is followed by upregulated expression of paracrine factors: nf-κb, tnf-α and il-1β genes in the ovary, which further activates the apoptotic cascade in the CYN-treated oocytes by upregulating p53, bax, casp3 and suppressing bcl2 gene expression. This revealed that cylindrospermopsin is an effective endocrine disruptor that induces reproductive toxicity by promoting oxidative stress and inducing early oocyte maturation by immune-activation of the NF-κB/TNF-α pathway, emphasising the importance of deciphering its ecotoxicological risk.