Investigation of the toxic mechanism of aspartame on female infertility using network toxicology and molecular docking approaches

Aspartame is a nonnutritive sweetener derived from phenylalanine and is widely used in food and beverages globally. In recent years, its safety, particularly the potential carcinogenic risks, has garnered significant attention; however, there has been relatively less focus on its potential infertility risks. This study employed network toxicology methods to construct an interaction network of aspartame and infertility-related targets and identify key targets and pathways. Subsequently, molecular docking technology was employed to further investigate the binding affinity and mechanism of action of aspartame with the key proteins. The results revealed that 46 shared targets between aspartame and female infertility were identified through public databases. Protein–protein interaction analysis further identified 4 key targets: interleukin-1 beta, angiotensin-converting enzyme 2, angiotensin-converting enzyme, and cathepsin S. Subsequent Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses indicated that these key targets were closely associated with the onset and progression of infertility. Molecular docking results showed that key targets – interleukin-1 beta, angiotensin-converting enzyme 2, angiotensin-converting enzyme, and cathepsin S – exhibited a high affinity for aspartame. This study systematically elucidates the potential for aspartame to affect infertility-related proteins, which may subsequently influence the female reproductive system by interfering with the function of biomolecules. Furthermore, this study introduces a novel scientific approach for evaluating the safety of food additives and provides a theoretical foundation for the development of public health regulations.