Germ cell risk assessment of combined exposure to monosodium glutamate and bisphenol A in male SD rat: deciphering the molecular mechanisms.

The present study evaluated the combined germ cell effects of monosodium glutamate (MSG) and bisphenol A (BPA) on juvenile Sprague Dawley rats. Animals were orally exposed to low and high doses of MSG and BPA, individually and in combination, for a consecutive duration of eight weeks. Combined exposure significantly reduced body weight and increased micronucleus formation, indicating systemic genotoxicity. Oxidative stress was demonstrated by elevated MDA, reduced GSH and catalase activity, and increased 8-OHdG expression. Sperm count, motility, chromatin integrity, and ultrastructure were significantly impaired. Histological and protein analyses confirmed testicular degeneration and molecular alterations. Hormonal imbalance was observed by decreased serum testosterone, LH, FSH, and reduced 17β-HSD expression, which suggested not only testicular dysfunction but also the involvement of the central hypothalamic-pituitary axis. Inflammation was evident with elevated TNF-α and testicular MPO activity, accompanied by activation of p-NF-κB p65/NLRP3/caspase-1/IL-18 axis. Bax-mediated apoptosis was elevated, while p-AMPK/AMPK downregulation suggested impaired energy metabolism. These findings demonstrated that combined MSG and BPA exposure induced oxidative stress, inflammation, apoptosis, and hormonal imbalance, leading to germ cell toxicity.