Study On The Molecular Mechanism Of The Orchitis Induced By Particulate Matter Exposure In Mice

Inhalable fine particulate matter usually refers to fine particulate matter(PM2.5)with an average diameter of less than 2.5 μm,which can be inhaled and deposited in the respiratory tract to cause disease.According to statistics,ambient air pollution causes more than 3 million deaths each year,which is one of the main factors causing the global burden of disease.After inhalable particles are sucked into the exchange area of the human lung,the ultrafine particles can reach various organs and tissues throughout the body through the blood circulation.When PM2.5 enters the human body,it can cause damage to the body and cells,mainly including inflammation,immune response,oxidative stress and DNA damage.Previous studies have found that excessive exposure to PM2 5 not only causes common lung damage and cardiovascular disease,but also may be associated with infertility in people of childbearing age.Because there are some reports that high-density ambient air pollution can cause male infertility,leading to a decrease in sperm count and semen quality,and also to varying degrees of damage to testis and reproductive-related cells.Therefore,we speculate that the adverse effects of excessive inhalation of particulate matter on the male reproductive system are related to the testis and cause orchitis.Orchitis refers to the acute or chronic inflammation of the testicles and is one of the main causes of male infertility.Although studies have shown that PM2.5 exposure is positively correlated with increased male infertility and orchitis,the molecular mechanism of testicular inflammation caused by PM2.5 exposure is unclear.In this paper,we successfully constructed the animal model of orchitis induced by PM2.5.In this model,while mice inhaled PM2.5 particles through the lungs to produce lung inflammation,it can also increase the lumen of the seminiferous tubules in the mouse testis,and the expression of related inflammatory genes in the testis also increased significantly.By analyzing the sperm quality of mice,we also observed that the total number of sperm in the PM2.5 exposed group was significantly reduced,and the abnormal morphological rate of sperm was significantly increased.When mouse Ledyig cells TM3 cells were stimulated with 200 μg/ml PM2.5,the expression levels of inflammatory genes such as Mcp1,IL6,Cxcl1 and Cxcl9 were significantly up-regulated,indicating that PM2.5 can stimulate TM3 cells to inflammatory response.Through the detection and screening of in vivo and in vitro samples,we found that PM2.5 exposure activates NF-κB signaling,which in turn activates the expression of downstream inflammatory genes regulated by the NF-κB signaling pathway.The release of excessive inflammatory factors breaks the testicular immune homeostasis,causing more immune cells to invade into the testicular seminiferous tubule lumen,leading to orchitis.When mice developed orchitis,their sperm count decreased significantly and the sperm deformity rate increased significantly.We further found that PDTC,an inhibitor of the NF-κB signaling pathway,can alleviate testicular inflammation caused by PM2.5 exposure.Considering that PM2.5 particles can cause severe inflammatory reactions in the testes of mice,and the treatment of inflammation can be treated by drug targeting,we speculate that in addition to specific inhibitors of the NF-κB signaling pathway,common clinical drugs may also have a relieving effect on PM2.5 exposure induced orchitis.Aspirin is currently the most widely used and low-cost non-steroidal drug in the world.In addition to being widely used in the prevention and treatment of cardiovascular diseases,it also has beneficial effects on human reproductive and reproductive diseases.We found that aspirin can reduce the expression of inflammatory genes in mouse Ledyig cells and reduce the inflammatory response of testicular and major organs in mice after PM2.5 exposure.Due to the alleviating effect of aspirin on PM2.5-induced orchitis in mice,the sperm count and abnormal rate of mice in the aspirin-treated group were improved.Therefore,we speculate that aspirin has a potential therapeutic effect on male reproductive problems caused by PM2.5.By studying the molecular mechanism of PM2.5 induced orchitis in mice,the key role of immune regulatory factors in the process of PM2.5 induced orchitis was found.At the same time,based on studying the toxicological effects of PM2.5 on the reproductive system of mice,this paper found that aspirin has a better relief effect on PM2.5-induced orchitis in mice,and has potential guidance for the clinical treatment of orchitis caused by environmental pollution.Further research is needed.