The Effect Of Fatty Acids On The Survival Rate Of Mouse Testis Support Cells And Its Mechanism

Object:Nowadays,accompanied with the economic development,obesity rate in the population elevated significantly.Meanwhile,the incidence of male infertility was also increased.Is there a relationship within the phenomenon remained unknown.A large sample study of us showed that both obesity related indexs and lipid in serum were not related with semen parameters.However,lipid in the seminal plasma showed a significant correlation with semen parameters,suggesting that testicular local lipid metabolism disorder is closely related to abnormal spermatogenesis.The mechanism is still unknown.Fatty acids,are important metabolic components in the body in the physiological condition.However,the rise of the saturated fatty acid was believed to be involved in many metabolic diseases such as diabetes,nonalcoholic fatty liver disease.The bodies with metabolic abnormalities were often accompanied with change in the composition and content of free fatty acids,including the elevation of saturated fatty acids and the decline of unsaturated fatty acids.At the same time,it has been reported that high concentration of saturated fatty acids can induce the apoptosis of testicular Leydig cells while unsaturated fatty acids have protective effect.Whether elevated free saturated fatty acids have an effect on other cells in the testes is unknown.Sertoli cells were the only somatic cells in the seminiferous tubule.Their function closely related with spermatogenesis.Researches have shown that spermatogenesis was decreased in mice with high-fat diet(HFD).Whether Sertoli cells were damaged was still unknown.Therefore,the object of this study was to explore the relationship between the fatty acids and testicular Sertoli cells to uncover the mechanism of HFD induced decreased spermatogenesis.Methods:1)Construction of high-fat diet(HFD)model,the parameters included testicular epididymal sperm count and testicular tissue TUNEL staining were performed and lipid content was detected.3)Construction of mice model with high saturated fatty acid.Epididymal sperm count,testicular local lipid content detection and testicular tissue TUNEL staining were evaluated.4)In vitro,saturated and/or unsaturated fatty acids were added to the culture medium of Sertoli cells,and the effect of different fatty acids on the viability of Sertoli cells were observed.5)A5/PI staining detection via flow cytometry was used to detect cell apoptosis.6)the apoptosis related genes and proteins were detected by RT-PCR and Westem-Blot.Results:1)Sperm count was decreased significantly in the HFD mice.Meanwhile,Testicular local free fatty acid accumulation and ROS levels elevated significantly.TUNEL staining showed that the apoptosis of Sertoli cells was significantly increased.PA,as a representative of saturated fatty acids,was used via intraperitoneal injection in the mice.As a result,sperm count declined significantly,local lipid accumulation level and testicular local ROS level were increased too.TUNEL staining showed the apoptosis of Sertoli cells was significantly increased.In vitro experiments we have demonstrated that saturated fatty acids would induce apoptosis of Sertoli cells,which may be related with the activation of ROS and subsequently activation of the Fas/FasL pathway.Fish oil(?-3 polyunsaturated fatty acids)would reverse the lipid toxicity of saturated fatty acids via its antioxidant ability.Conclusion:HFD may be related to the decline of male fertility.Elevated saturated fatty acids,declined polyunsaturated fatty acids and injuried Sertoli cells may be involved in the process.In clinical,men of childbearing age should be encouraged to maintain good habit.Avoid food with high fat and the therapies for the regulation of lipid content should be considered.The application of ?-3 polyunsaturated fatty acids may improve the microenvironment of male testicular spermatogenesis.