Microplastics–Induced Male Reproductive Toxicity Via Modulation of Steroidogenic Genes and Testicular Tissue Alterations in the Mouse Model: In Silico and In Vivo Approaches

Microplastics are emerging environmental contaminants with increasing evidence of reproductive toxicity. This study investigated the different effects of polystyrene microplastics (PSµPs) on male reproductive function and evaluated the protective role of taurine (Taur) in Swiss mice using integrated in silico and in vivo approaches. Adult mice were orally exposed to PSµPs (10 mg/kg) for eight weeks, with or without Taur supplementation (200 mg/kg). PSµPs exposure resulted in marked reproductive toxicity, evidenced by significant reductions in gonadosomatic index, testicular weight, and testosterone levels, along with disruption of LH and estradiol balance. Moreover, PSµPs induced severe oxidative stress, as evidenced by significant declines in SOD, CAT, and GPx activities and an increase in MDA levels. At the molecular level, PSµPs caused pronounced downregulation of key steroidogenic genes ( STAR , CYP11A1 , CYP17A1 , CYP19A1 , and HSD17B3 ) compared to controls. Histopathological analysis revealed extensive testicular degeneration, increased apoptosis (elevated cleaved caspase-3), and reduced cell proliferation (decreased PCNA expression). Importantly, Taur co-administration significantly attenuated these adverse effects, restoring antioxidant defenses, partially normalizing hormone levels and gene expression, and improving testicular architecture. In silico docking further supported these findings by demonstrating strong interactions between styrene and the protein products of mRNAs involved in steroidogenesis, suggesting potential binding affinities. Overall, this study highlights that PSµPs induce severe testicular dysfunction through oxidative stress–mediated and gene regulatory mechanisms, while taurine exerts a potent protective effect via antioxidant, anti-apoptotic, and endocrine-modulatory pathways. These findings provide novel insights into microplastic-induced reproductive toxicity and propose taurine as a promising therapeutic strategy.