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NF-κB-Associated Redox Signaling and Intrinsic Apoptotic Activation in Polystyrene Nanoplastic–Induced Testicular Toxicity and Modulatory Effects of Nelumbo nucifera
Summary
Researchers exposed rats to polystyrene nanoplastics for 55 days and found impaired sperm quality, reduced testicular weight, elevated NOX4 and NF-κB signaling, and activation of the intrinsic mitochondrial apoptosis pathway — with co-administration of Nelumbo nucifera rhizome extract substantially attenuating these reproductive and epigenetic disruptions.
Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants increasingly linked to male reproductive toxicity; however, the molecular mechanisms underlying testicular damage remain unclear. This study evaluated PS-NP-associated testicular damage in rats after 55 days of exposure and assessed the modulatory effects of Nelumbo nucifera leaf, flower, and rhizome extracts, with quercetin as a reference. PS-NP exposure reduced spermatogenic cell populations, testicular, epididymal weights, and sperm motility. These changes were accompanied by increased NOX4 and NF-κB expression, upregulation of intrinsic apoptosis-related genes (Tp53, Bax, Caspase-9, and Caspase-3), elevated caspase-3 and caspase-9 protein levels, and enhanced cleaved caspase-3 immunoreactivity. In contrast, Fas and Caspase-8 were downregulated, confirming intrinsic mitochondrial apoptosis. PS-NP exposure also altered reproductive hormone receptor expression (LHr, FSHr, and AR) and dysregulated chromatin-regulatory genes, with increased Dnmt1, Dnmt3a, and Ehmt2 (G9a) and decreased Hdac1 and Ep300. Co-administration of N. nucifera attenuated most of these alterations, with the rhizome extract exhibiting the most pronounced protective effect. GO and PPI network analyses suggested functional connectivity among stress-responsive, apoptotic, and chromatin-modifying proteins. Docking simulations indicated phytochemical-apoptosis-related protein interactions. PS-NPs may impair testicular homeostasis through coordinated stress, apoptosis, endocrine disturbance, and epigenetic dysregulation, with possible relevance to male reproductive health, while N. nucifera shows promise as a protective modulator.