Ivermectin effects in cultured endothelial cells from porcine corpus luteum

Ivermectin (IVM), a widely used antiparasitic, raises emerging concerns regarding reproductive toxicity. This study investigated the effects of clinically relevant IVM concentrations (20, 40, 60 ng/mL) on endothelial cells from porcine corpus luteum, a translational model for vascular function. Proliferation and metabolic activity were assessed via BrdU ELISA and ATP bioluminescence assay, VEGF-A secretion by ELISA, redox status through superoxide and nitric oxide, FRAP assay, and SOD activity by colorimetric methods. IVM significantly impairs endothelial homeostasis by inhibiting proliferation (p<0.05) and suppressing VEGF-A production at higher doses (p<0.05), despite a compensatory increase in metabolic activity. IVM induced a biphasic nitric oxide effect (p<0.01) and elevated superoxide levels (p<0.05), causing oxidative DNA damage (p<0.001) and upregulating antioxidant defenses (p<0.05), while autophagosome load remained unchanged. These findings indicate potential risks to mammalian fertility through functional impairment of the corpus luteum microvasculature.