Silk Fibroin Encapsulated Icariin Nanoparticles Mitigate Bisphenol A-Induced Spermatogenesis Dysfunction

Bisphenol A (BPA) is a prevalent endocrine disruptor found in natural environments. Exposure to BPA has been associated with male infertility. The natural phytochemical icariin (ICA) has demonstrated significant promise for the treatment of male infertility. However, its effectiveness is limited due to its low bioavailability, poor water solubility, and insufficient targeting abilities. Herein, novel nanoparticles are generated from the natural silk fibroin, which are used to load ICA. The efficient drug delivery system (ICA-SNPs) result in significantly focused drug distribution to spermatogonium, enhancing the anti-infertility properties of ICA, and can effectively mitigate spermatogenesis dysfunction induced by BPA, control serum sex hormone levels, and enhance testicular ultrastructure. Additionally, the ICA-SNPs restore spermatogenesis dysfunction primarily via the hormone biosynthesis, spermatogonium meiosis process, and glycerophospholipid metabolism. Incorporation of icariin (ICA) into regenerated silk fibroin-based nanoscale drug delivery systems using self-assembly procedures is proposed to develop an efficient drug delivery system (ICA-SNPs) in testicular tissue. The combined analysis of transcriptomics, proteomics, and metabolomics data reveals that ICA-SNPs effectively counteracts the spermatogenesis impairment induced by BPA in mice via the regulation of spermatogonium meiosis process, and glycerophospholipid metabolisms.image