Acrylamide-Induced Neuroendocrine Disruption in Adult Male Zebrafish (Danio rerio): Mechanistic Insights into...

Acrylamide (AA), a well-documented neurotoxin and reproductive toxicant in mammals, poses a potential risk to teleost species, yet its impact on the hypothalamic-pituitary axis and neuroendocrine integrity remains insufficiently explored. This study hypothesises that AA exposure disrupts locomotor behaviour, neurotransmitter homeostasis, and neuroendocrine regulation in adult male zebrafish, impairing reproductive fitness. Using 72 h exposure to 0.5 and 0.75 mM AA, we demonstrate significant alterations in acetylcholinesterase activity, dopamine levels, and Nos1 expression, correlating with locomotor and behavioural deficits. A marked decline in c-Fos immunoreactivity further suggests compromised neuronal activation associated with impaired mating behaviours. Notably, AA perturbs brain neuroendocrine gene expression, including kisspeptins (kiss1, kiss1rb, kiss2, kiss1ra), gnrh3, gonadotropins (fshb, lhb), estrogen receptors (esr1, 2a, 2b), and steroidogenic markers (cyp11a1, cyp17, hsd3b, cyp19a1b), corroborating well with reduced fertilisation efficiency. Mechanistically, oxidative stress characterised by elevated ROS and lipid peroxidation (MDA levels), dysregulated antioxidant systems (catalase, GST, Nox4, Nrf2/Keap1), and altered Cox2 expression drives JNK phosphorylation (activation), Bax/Bcl2 imbalance, Caspase activation, Parp1 cleavage, and DNA fragmentation, triggering brain apoptosis. Intriguingly, increased CD206 and Il-10 expression alongside suppressed proinflammatory mediators potentially hint at altered microglial polarisation and immune modulation in AA-treated brains. While current findings highlight AA-induced neurotoxicity and neuroendocrine disruption in zebrafish, in silico network toxicology analysis could identify AA-susceptible overlapping molecular targets and brain pathways impacting human neuronal and reproductive health. This study offers critical insights into the mechanistic basis of AA toxicity and its relevance in environmental health risk assessment.