Study On The Mechanism Of Fenvalerate Induced Reproductive Injury In Male SD Rats

Objective:To investigate the mechanism of Fen interfering with reproductive endocrine function and inducing apoptosis of spermatogenic cells in male SD rats.Methods:The doses of fenvalerate exposure in rats were determined by preliminary experiments.In the formal experiments,24 adult male SD rats were randomly divided into control group(0 mg/(kg.d)),low-dose Fen exposure group(20 mg/(kg.d)),high-dose Fen exposure group(40 mg/(kg.d)),and 8 rats in each group.The Fen-exposed groups were given the same volume of Fen solution with different concentrations by gavage,and the control group was given the same volume of corn oil as the Fen-exposed group,the rats were gavaged once a day for 30 consecutive days.The sperm count,sperm motility and sperm deformity rate were detected by optical microscope;The levels of serum Gn RH,LH,FSH,T,E2 and testicular T,E2,INH-B,ROS,MDA were determined by ELISA;RT-q PCR and Western bolt were used to detect the m RNA and protein expression levels of FSHR,LHR,AR,ERβ,ABP,STAR,3β-HSD,CYP11A1,CYP19A1,Bax,Bcl-2,Cyt c,Caspase 3 and Caspase 9;Pathological changes of testis and epididymis were observed by HE staining;TUNEL was used to detect the apoptosis of germ cells in testis of male rats;The number of Leydig cells in testes was detected by immunofluorescence.Results:(1)The results of the sperm,testis and epididymis injury of male SD rats by Fen showed that compared with the control group,the number of sperm decreased,sperm motility decreased and sperm deformity rate increased in the 40 mg/(kg.d)Fen-exposed group(P < 0.05 or P < 0.01);the number of spermatogenic cells in the seminiferous tubules of rats decreased,and the spermatogenic cells were missing to varying degrees,the epididymal epithelium was thickened,the number of epithelial cells increased,and the number of sperm in the lumen decreased in the Fen-exposed group.(2)The results of Fen interfering with reproductive endocrine function in male SD rats showed that compared with the control group,the contents of Gn RH and E2 in serum and E2 and INH-B in testis of rats significantly increased in 40 mg/(kg.d)Fen-exposed group(P <0.05 or P <0.01),the content of T in serum and testis decreased significantly(P< 0.01,P < 0.05);the expression levels of AR,ERβ,ABP and CYP19A1 in the testes significantly increased(P < 0.01),the expression levels of St AR,3β-HSD and CYP11A1 significantly decreased(P < 0.01);the number of Leydig cells decreased significantly(P <0.01).(3)The results of Fen induced apoptosis of spermatogenic cells showed that compared with the control group,the number of apoptotic germ cells in the testes of male rats increased significantly in the 40 mg/(kg.d)Fen-exposed group(P < 0.01),and the contents of ROS and MDA in the testes significantly increased(P < 0.01);the expression levels of Bcl-2 in the testes significantly decreased(P < 0.01),and the expression levels of Bax,Cyt c,Caspase 3,Caspase 9 in the testes significantly increased(P < 0.01).Conclusions:(1)Fen can inhibit the expression of T synthesis related proteins and enzymes and induce Leydig cells injury,reduce the ability of T synthesis in rats,at the same time,up regulate the expression of aromatase in the testes of male rats,promote the transformation of T to E2,lead to the change of T and E2 content,resulting in reproductive endocrine disorder in male rats;(2)Fen may stimulate the production of reactive oxygen species in testes,and further cause mitochondrial damage,resulting in excessive apoptosis of germ cells,hindering spermatogenesis,and eventually lead to reproductive damage in male rats.