Swainsonine induces granulosa cell apoptosis and steroidogenic impairment associated with oxidative stress and...

Swainsonine (SW), the principal toxic alkaloid of locoweeds, causes significant reproductive failure in grazing livestock, but its direct cellular targets and mechanisms remain poorly defined. This study aimed to elucidate the cytotoxic effects of SW on goat ovarian granulosa cells (GCs) and the underlying molecular pathways. Based on an initial cytotoxicity profile (24 h IC₅₀ = 21.79 μM), GCs were treated with 20 μM SW for 24 h to investigate mechanistic endpoints. SW exposure significantly suppressed cell proliferation, induced G0/G1 phase arrest, and triggered apoptosis. This was associated with a state of severe oxidative stress, characterized by elevated reactive oxygen species (ROS), glutathione depletion, increased lipid peroxidation, and loss of mitochondrial membrane potential. Concurrently, SW inhibited the secretion of estradiol and progesterone, downregulating key steroidogenic genes (STAR, CYP19A1, HSD3B1). Transcriptomic analysis revealed enrichment of pathways related to oxidative stress, apoptosis, and cell cycle regulation, and suggested the involvement of MAPK signaling. Our integrated analysis reveals that SW exposure induces oxidative stress, mitochondrial dysfunction, cell cycle arrest, apoptosis, and suppressed steroidogenesis in goat GCs. Transcriptomic profiling further implicates pathways related to oxidative stress and apoptosis. These findings suggest a mechanistic framework in which oxidative stress and mitochondrial dysfunction are central to SW-induced ovarian toxicity, although the precise causal relationships require further validation.