Silk fibroin microneedles loaded with epigallocatechin gallate mitigate atrazine-induced testicular toxicity

Abstract

Atrazine (ATZ), a commonly used herbicide, disrupts male endocrine systems, impacting reproductive health. Epigallocatechin gallate (EGCG) possesses potent antioxidant properties and shows promise in alleviating testicular dysfunction induced by endocrine disruptors. However, its clinical utility is hindered by poor physicochemical stability and low oral bioavailability. Herein, we first developed a silk fibroin microneedles (MNs) patch loaded with EGCG, enabling EGCG to directly target the testes through transdermal administration. Our findings revealed that EGCG-loaded silk fibroin microneedles (EGCG-SF-MNs) exhibited excellent biocompatibility with no observed cytotoxicity in vitro or in vivo. In vitro assays revealed that EGCG-SF-MN patches significantly reduced ATZ-induced apoptosis and oxidative stress in GC-1 spg cells by modulating the Bcl-2/Bax ratio and ROS levels. In vivo studies in rats further confirmed the therapeutic potential of these patches, as they reversed ATZ-induced testicular dysfunction, sperm abnormalities, and blood-testis barrier disruption. Proteomics analysis highlighted the beneficial effects of EGCG-SF-MN patches on restoring protein expression altered by ATZ, particularly in necroptosis and lysosome pathways. Collectively, the development of EGCG-SF-MNs demonstrates enhanced therapeutic and targeted delivery efficacy for potential clinical applications in treating male reproductive disorders induced by environmental endocrine disruptor ATZ.

Keywords: Apoptosis; Atrazine; EGCG-SF-MNs; Epigallocatechin gallate; Necroptosis.