Early brain gene network alterations and growth disruptions in juvenile Chinese longsnout catfish (Leiocassis longirostris) induced by 17β-estradiol and 17α-methyltestosterone

Abstract

Endocrine-disrupting chemicals (EDCs) 17β-estradiol (E2β) and 17α-methyltestosterone (MT) have been detected in aquatic environments at concentrations capable of perturbing neuroendocrine systems, yet their molecular mechanisms of action remain incompletely characterized. This study investigated the effects of chronic exposure to E2β and MT on brain development and neuroendocrine regulation in Leiocassis longirostris, a commercially important catfish species endemic to the Yangtze River Basin. Juvenile fish were exposed to three nominal dietary doses (100–300 ng) of each hormone for 30 days, corresponding to waterborne concentrations (556–1667 ng/L) within the upper range of environmental detections. Histopathological analysis revealed dose-dependent plasma accumulation in cerebral microvasculature, indicative of compromised blood-brain barrier integrity. Transcriptomic profiling identified significant suppression of immediate early genes (IEGs) critical for synaptic plasticity, including FOS, JUN, EGR1, NR4A1, CEBP-A/D, and ETS1, with E2β exerting stronger inhibitory effects (maximal at 200 ng-dose). Concomitant upregulation of neuroendocrine genes cga (gonadotropin α-subunit) and pomcb (pro-opiomelanocortin) suggested compensatory endocrine feedback mechanisms. Growth inhibition was observed in both treatment groups, with E2β-induced reductions in body weight exceeding those of MT. Functional enrichment analysis linked these transcriptional changes to disrupted pathways in synaptic signaling, chromatin remodeling, and endocrine regulation. Collectively, these findings demonstrate that estrogenic and androgenic EDCs impair neurodevelopmental processes via suppression of IEGs, leading to growth retardation and endocrine dysregulation. This study underscores the sublethal risks posed by sex steroid EDCs to wild fish populations and highlights the need for targeted regulatory measures to mitigate aquatic endocrine disruption.