Studies On Male Reproductive Toxicity And Mechanism Of Action Of THH

In this experiment,100male SD rats were randomly divided into5.0g/kg,10.0g/kg,20.0g/kg drug group and normal control group (distilldwater),to THH gavage for3months, in the administration of1months,2months,3months and recovered1months were measured body weight,organ weight, detecting the testis homogenate related enzymes, serumhormone levels and light microscopy and transmission electron microscopyultrastructural observation.Results：1.THH continuous exposure of3months,It has a certain role inpromoting the growth of body weight of rats; testis, epididymis of rat canmake obvious atrophy. It is showed that the atrophy degree may beassisciated with exposure times and dose.(howed a significant dependence.)2.After administration of THH3months, it can make the function ofrat testis marker enzyme activity change.It is showed that increasing ALP,LDH activity,reduce the LDH-X, SDH activity, and stop the THH exposurehas not been restored after1months,the ACP, ATPase activity wasdecreased first and then increased, no obvious effect on the SOD activity of the rat testis s, but the THH had decreased the content of MDA in rat testis.3.In middle and high dose group, after administration of THH3months, the serum T level of rats decreased significantly, while the lowdose group after2months, the serum T level higher than that of the controlgroup; after2months, the serum E2level in rats was increased with acertain degree.4.THH can lead to pathological change. Light microscopicexamination is found that spermatogenic cells reduced and disappearedmainly, and aslo atrophy of seminiferous tubules in the epididymal spermdecreased or disappeared. Testicular ultrastructural have changed includingspermatogenic cell necrosis, vacuolation and deletion, lysosomes,mitochondria swelling,pycnosis, dilated endoplasmic reticulum, nuclearchromatin anomaly distribution or dissolution.Conclusion:1.THH exposed for3months can reduce the level of testosterone, buttestosterone decrease does not result in testis of rats exposed to THHrefined inhibition mainly.2.THH can lead to abnormal testicular function of marker enzymes,functional marker enzyme caused abnormal germ cell structure andfunction change.3.THH may reduced and disappeared the seminiferous tubule atrophyof testis spermatogenic cells changed obviously; and also on the change of ultrastructure of testis.4.THH exposure may lead to the target organ on malereproductivetoxicity in rats is testis.firstly,the main target cell is the firsttesticle; then spermatogenic cells, followed by the supporting cells; Itstargets site is the mitochondria of the cells,it can caursed mitochondrialswelling, condensation and pathological changes in cellular energymetabolism, and leading to alterations in cell structure and function oftestis, which is the direct cause of male reproductive toxicity.5.There was no significant correlation between THH malereproductive toxicity and oxidative damage mechanism.6.From the test results, Our experiment indicated that the index oftestis and epididymis, testis homogenateindex, LDH-X activity and LDH-Xratio may be a screening target of THH drugs reproductive toxicity in vivo.