Zinc and Lead Impair Steroid-Driven Oocyte Maturation Through Nrf2-Metallothionein and cAMP Signaling in Mystus vittatus (Bloch, 1794): Insights From an In Vitro Study.

The present study emphasizes the cAMP-dependent signaling pathway, germinal vesicle breakdown (GVBD), and the role of the Nrf2-metallothionein (MT) system under metal-induced oxidative stress. It compares how zinc (Zn) and lead (Pb) affect steroid-driven oocyte maturation in the freshwater catfish Mystus vittatus via in vitro exposure of oocytes to inhibitory concentrations (1/10 IC₅₀: ZnSO₄ at 3.9 μM, Pb (NO₃)2 at 2.4 μM). Measurements included reactive oxygen species, Ca2+, cAMP-protein kinase A, maturation-inducing hormone (MIH), MT, estradiol receptor α, cyclin B-Cdc2, and the nuclear factor erythroid 2-related factor 2 and Kelch-like ECH-associated protein 1 pathway. Exposure of oocytes to Zn and Pb significantly (p < 0.05) reduced GVBD, MIH, and Ca2+ levels, whereas estradiol and ERα remained unchanged. Pb exposure significantly (p < 0.05) elevated cAMP and PKA. Cyclin B and Cdc2 protein levels significantly (p < 0.05) dropped in metal-exposed oocytes. Both metals significantly (p < 0.05) increased ROS, with Pb inducing greater. MT and nuclear Nrf2 expression increased significantly (p < 0.05), whereas cytosolic Keap1 significantly (p < 0.05) declined, most markedly with Pb. Statistical analyses, including ANOVA, correlation, principal component analysis (PCA), and random forest model (RFM), were performed to understand the redox-regulatory mechanisms of the oocyte maturation pathway in distinct, metal-specific ways: Pb more strongly impaired steroid-mediated oocyte maturation than Zn. PCA and RFM highlighted increased ROS, Nrf2, cAMP, and MT, with decreased MIH-MPF components, indicating that metal-induced redox activation up-regulated the Nrf2-MT pathway while suppressing maturation signals, thereby delaying oocyte maturation.