Effects Of Exercise Intervention On MOTS-c And Testosterone Biosynthesis In Testicular Tissue Of Male Mice And Its Mechanism

Objective:In order to explore the effect of obesity and weight loss by exercise on the reproductive function of male mice and the mechanism,exercise intervention was applied to obesity mice model after high-fat diet was prepared.To observe the relationship between the changes of MOTS-c and ERK1/2 in testis tissue,St AR/P450scc/3β-HSD,the key enzyme of testosterone synthesis,and male reproductive function after obesity and exercise weight loss in mice,which provided experimental basis for revealing the mechanism of obesity male reproductive function hypofunction and theoretical basis for exploring effective prevention and treatment methods.Methods:Five-week-old male C57BL/6 mice(n=24)were randomly divided into normal control group(NC,n=8)and obesity group(HF,n=16),fed with high-fat diet.After 10 weeks,4 obesity resistant mice were excluded,and the other HF mice weighed more than 20% of the weight of the NC group,which indicated obesity model was successfully established.HF group was randomly divided into obesity control group(HC,n=6)and obesity exercise group(HE,n=6),and continued to be fed with high-fat diet.Exercise intervention was 6 days/week and lasted for8 weeks.The running speed and exercise time showed an increasing trend,with a constant load from the third week to the eighth week,60 minutes and a running speed of 15m/min.Samples were taken after the intervention.Immunohistochemistry was used to detect the expression of MOTS-c in testis tissue,ELISA was used to detect the content of testosterone,MOTS-C in serum and MOTS-C in testis tissue,real-Time PCR and Western-Blot were used to detect the mRNA and protein expression levels of ERK1/2,St AR,P450 scc and 3β-HSD in testis tissue.Results:1.Compared with NC group,the body weight,Lee’s index,weight of testis,seminal vesicle and epididymis in HC group increased significantly(P < 0.01,P < 0.01,P < 0.05).However,the testis coefficient,epididymal coefficient and seminal vesicle coefficient decreased significantly(P < 0.01,P < 0.05,P < 0.05),serum testosterone,MOTS-c content and sperm motility of mice decreased significantly(P < 0.01),mRNA and protein expressions of St AR,P450 scc,3β-HSD and MOTS-c in testis tissue decreased significantly(P < 0.01,P < 0.05),and p-ERK1/2 protein expression increased significantly(P < 0.01).2.Compared with HC group,the body weight,Lee’s index,testis,epididymis and seminal vesicle coefficients,serum MOTS-c,testosterone content and sperm motility of HE group mice were significantly decreased(P < 0.01,P < 0.01,P < 0.05).The mRNA and protein expressions of St AR,P450 scc,3β-HSD and MOTS-c in testis tissue were significantly increased(P < 0.01),and the expression of p-ERK1/2 protein was significantly decreased(P < 0.05).Conclusion:1.Obesity in early development of male mice may have negative effects on male reprodu ctive function by down-regulating MOTS-c expression in Leydig cells,activating ERK1/2phosphorylation,inhibiting transcription and translation of testosterone synthase,and redu cing testosterone synthesis and secretion.2.Eight-week treadmill exercise can effectively improve the obesity of male mice,up-reg ulating the expression and content of MOTS-c in Leydig cells,inhibiting ERK1/2 activati on,promoting the expression of key enzymes in testosterone synthesis,and improving th e negative effects of obesity on male reproductive function.