Curcumin Attenuates Glyphosate-Induced Mammary Toxicity via Suppression of ER Stress and the TNFα/MAPK/STAT3 Axis

Curcumin, a natural polyphenol with well-established antioxidant and anti-inflammatory properties, was evaluated for its protective effects against glyphosate (GLY)-induced mammary toxicity. Pregnant mice received GLY (50 or 250 mg/kg/day) with or without curcumin (150 mg/kg/day) by oral gavage; GLY dose-dependently disrupted alveolar architecture, caused marked inflammatory infiltration, and downregulated tight-junction proteins. In parallel, goat mammary epithelial cells (GMECs) were treated with GLY (1 or 7 mM) and curcumin (1 µM) to dissect acute cellular stress pathways. These complementary models address distinct aspects of GLY toxicity: the in vivo system reflects defined oral exposure, whereas the in vitro setting employs high concentrations to probe mechanistic events. Transcriptomic profiling combined with functional assays demonstrated that GLY triggered oxidative stress, endoplasmic reticulum stress, and intracellular Ca²⁺ overload, activated the TNFα/MAPK axis, suppressed STAT3 phosphorylation, and ultimately promoted apoptosis. Curcumin co-treatment alleviated these alterations at both structural and molecular levels. These findings indicate that curcumin can combat GLY-induced mammary injury by restoring cellular homeostasis and inhibiting apoptotic and inflammatory signaling, thereby protecting breast health.