Cadmium-Induced Male Reproductive Toxicity:The Role Of FYN/Arp3 Protein Complex

Cadmium is a toxic heavy metal found in the environment and is considered one of the major reproductive toxins for males.It does not have any biological function in humans.In the body,cadmium can accumulate in numerous organs and cause impairment in their functions（such as the liver,kidney,and testis）because of its relatively long biological half-life and very low excretion rate.A decline in male fertility is primarily a result of a decline in sperm count and quality of semen.There are multiple mechanisms that contribute to cadmium’s reproductive toxicity in men,including damage to the vascular system of the testis,damage to the blood-testis barrier,toxic effects of germ cells,destruction of the cytoskeleton,oxidative stress,and cell death.It may result from a particular action or from a combination of actions.FYN is a non-receptor tyrosine kinase of the SRC family that facilitates virus entry across epithelial tight junctions.The role of FYN in mammalian testes in maintaining the blood-testis barrier（BTB）integrity and adhesion of germ cells to Sertoli cells is not well defined,nor is it known if it contributes to exposure to cadmium.To further study the expression and localization of FYN in the testis,male ICR mice（aged 2–10 weeks）were used as experimental subjects.According to our findings in this study,the FYN is a component of the BTB and the apical ectoplasmic specialization（ES）at Sertoli-Sertoli and Sertoli-spermatid interfaces,respectively,and is expressed extensively in mouse testes during postnatal development.FYN was shown to be structurally linked to the actin and microtubule-based cytoskeletons.CdCl₂（3 mg/kg·body weight）was injected intraperitoneally into adult mice to simulate the symptoms of acute cadmium toxicity,and this in vivo model was used to explore the modulatory effect of FYN on BTB and apical ES dynamics within the testes.We found that the FYN/Arp3 protein complex is an important regulator of cadmium male reproductive toxicity.The CdCl₂-induced epithelial restructuring was associated with a transient increase in the interaction between FYN and the actin branching/nucleation protein Arp3,as well as an induction of Arp3 phosphorylation,which lead to actin cytoskeleton remodeling,resulting in BTB damage and germ cell loss in the seminiferous epithelium.Based on the results,we propose a model in which FYN and Arp3form a protein complex that is responsible for junction reorganization events at the apical ES and the BTB in cadmium-induced male reproductive toxicity.This mechanism could also provide a pathway for virus entry into the immunoprivileged testicular microenvironment through the BTB,which would lead to further research in the future.