Integrated Targeted and Untargeted Metabolomics Reveals the Toxic Mechanisms of Zearalenone in Goat Leydig Cells
Year: 2026
Type: article
Abstract: AbstartZearalenone (ZEA) is a mycotoxin commonly found in animal feed and is associated with pronounced reproductive toxicity. However, most studies on ZEA’s reproductive effects have focused on female monogastric animals, while research on male ruminants remains limited. This study aimed to investigate the cytotoxic and metabolic mechanisms underlying ZEA-induced damage in goat Leydig cells (LCs). The CCK-8 assay was first used to determine the effective ZEA concentration (IC50 ≈ 20 μM), and a cytotoxicity model was subsequently established. The model’s validity was confirmed using qRT-PCR, transmission electron microscopy, flow cytometry, and JC-1 staining. Results showed that ZEA significantly reduced LCs viability in a dose-dependent manner, decreased mitochondrial membrane potential, induced cell cycle arrest, and triggered apoptosis. Targeted and untargeted metabolomics analyses revealed that ZEA disrupts steroidogenic pathways and alters steroid hormone secretion, resulting in elevated levels of progesterone, corticosterone, and androstenedione, and reduced dihydrotestosterone levels. Furthermore, 52 significantly altered metabolites were identified, predominantly enriched in glycerophospholipid metabolism, choline metabolism, and neurotransmitter vesicle pathways, with corresponding changes in gene expression. Collectively, these findings provide novel mechanistic insights into ZEA-induced reproductive toxicity in male ruminants, underscore the link between metabolic dysregulation and reproductive impairment, and offer a foundation for evaluating ZEA’s impact on goat reproductive performance.
Source: Animals
DOI: 10.3390/ani16020283
Institution: Guizhou University
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,896
Awards: G1200755013, G1747218003, G4567164577
OpenAlex ID: W7124419728