Exposure To The Organic Sulfur Fungicide Captan Affects Ovarian Function And Oocyte Development In Mice

Captan is an organic sulfur fungicide that belongs to the phthalimide family.It is the most widely used non-systematic fungicide in modern agriculture and its residues have been found in the environment and food.Previous studies reported captan could exert multiple toxicities on tissues,but it is still unclear about the toxicity of captan on the mammalian female reproductive process.Female reproduction is the essential physiological pathway for species reproduction,including endocrine regulation of oogenesis,follicle formation and development,oocyte meiosis maturation,fertilized egg formation and implantation,embryo formation and development,etc.Maintaining normal reproductive development depends not only on genetic factors but also significant measures on environmental factors.Environmental pollution exposure may cause damage to every link of the reproductive process,resulting in reduced fertility,fetal growth retardation,miscarriage,and birth defects.In our present study,captan was selected to establish a mouse toxicity model with gavage.We found that captan could reduce the weight and ovarian coefficient of mice,and interfered with the expression of estrogen receptors,which in turn affected the development of follicles,and ovarian granulosa cells from the captan exposure group experienced a high level of apoptosis.Through transcriptome analysis,we found that captan exposure altered the expression of multiple oocyte genes related to autophagy,apoptosis,and endoplasmic reticulum stress.We also showed that oocyte number reduced and maturation competence decreased.Western blot,Quantitative Real-time PCR,Immunohistochemistry and Immunofluorescence staining results showed that captan exposure could induce follicular development disorders,disrupted the expression of female hormone receptors,apoptosis of granulosa cells,accumulation of inflammatory factors and decreased oocyte quality.Moreover,captan exposure could increase oxidative stress and mitochondrial dysfunction,as indicated by increased ROS level,suboptimal mitochondrial structure and distribution,and depolarized potential.Besides,captan would trigger DNA damage,autophagy and early apoptosis,showing with emerging ?-H2 AX,LC3and Annexin-V signals and increased related genes.Taken together,our results indicated that captan exposure impairs ovarian homeostasis and subsequently affects oocytes development.