The Application Of Small Molecule SM1 In Chronic Orchitis

Orchitis is an important factor in male infertility.Male infertility caused by orchitis is approximately 6-15%,and it is as high as 30%in areas with limited medical services.Especially,chronic orchitis accounts for the majority of orchitis pathology compared to acute orchitis.Chronic orchitis is an inflammatory disease of testis caused by a variety of pathogenic factors.The duration of the disease is generally more than three months.The pathological phenotype is generally increased lymphocyte infiltration around the seminiferous tubules and associated seminiferous tubule damage.Male fertility is affected and even leads to male infertility.It is currently believed that for patients with symptoms of chronic infection and detection of pathogenic microorganisms,treatment standards related to the use of antibiotics and acute infection can be followed.At present,it is believed that for patients with chronic infection symptoms and detection of pathogenic microorganisms,and the treatment standards related to acute infections are followed.However,after discontinuing the medication,patients may still experience leukocytospermia or even azoospermia.This result suggests that chronic orchitis cannot be easily cured.So,there is no standardized clinical treatment guideline for chronic orchitis.Urgently a new and effective treatment method is developed.Organoids not only can better simulate the tissue structure and physiological environment in vivo,but also show great potential in the application of disease simulation and drug screening.This study is based on the testicular organ models for drug screening.And chronic orchitis mouse models were combined,to verify the therapeutic effect of small molecule drug SM1 on improvement of testicular and chronic orchitis mice microenvironment and spermatogenic function.The main research contents and results are as follows:First,according to the comparisons between testicular organs and testicular cells in vivo,the disorders of microenvironment in testicular organs were revealed and verified.Subsequently,the small molecule SM1 was screened through the haploid production as the final criterion.It can improve the microenvironment of testicular organs,the effciency of spermatogenesis and the semen quality.Secondly,the effectiveness of small molecule drug SM1 in improving chronic orchitis was verified by two chronic orchitis mouse models.A bilateral vasectomy model and an experimental autoimmune orchitis(EAO)model were constructed.And they were verified for typical pathological features of chronic orchitis.Subsequently,the chronic orchitis mouse model was treated with small molecule SM1 by intragastric administration.It confirms that small molecule SM1 can reduce the expression of proinflammatory cytokines and improve collagen deposition.At the same time,small molecule SM1 can significantly increase the number of germ cell at all levels,the embryonic development rate and offspring live rate.The above results suggest that small molecule SM1 can effectively improve the testicular microenvironment and spermatogenic function.This provides a new therapeutic option and clue for the treatment of chronic orchitis.In conclusion,the small molecule SM1 was screened by the testicular organoid platform.Through the validation of two classic chronic orchitis animal models,it was confirmed that SM1 can effectively improve the pathological changes in chronic orchitis.This study plays an important role in promoting the development of clinical treatment research.