Role Of Neuropathy Target Esterase In Tri-ortho-cresyl Phosphate Inhibiting Spermatogenesis In Mice

Objective: Tri-ortho-cresyl phosphate (TOCP) has been widely used asplasticizers, plastic softeners, and flame-retardants in the industry. The aim of thestudy is to observe the effect of TOCP on testicular seminiferous tubules andspermatogenesis in mice, and investigate the role of neuropathy target esterase (NTE)in TOCP inhibiting spermatogenesis in mice.Methods:1. HE staining was utilized to observe the effect of TOCP on testicularseminiferous tubules and spermatogenesis in mice.2. Immunohistochemistry wasused to identify the expression of NTE in the mice testis.3. Phenyl valeratehydrolysis was utilized to measure the effect of TOCP on the NTE activity in the micetestis.4. RT-PCR was used to investigate the effect of TOCP on the level of NTEmRNA in the mice testis.Results:1. The male mice were administrated with different concentrations ofTOCP (0,100,200,400mg TOCP/kg/day) for14d. Compared with the control group,the200mg and400mg TOCP/kg/day group significantly decreased the weightcoefficient of testis (P＜0.05), while the100mg TOCP/kg/day groups not. Thedifferent concentrations of TOCP (0,100,200,400mg TOCP/kg/day) could notsignificantly decrease epididymis coefficient (P>0.05).2. In mice receiving200mgand400mg TOCP/kg/day group, the seminiferous tubule showed disorganizedhistoarchitecture and germ cell depletion. While in the100mg TOCP/kg/day groups,no morphologic changes of the seminiferous epithelium were noted. Compared withthe control group, there was a significant decrease in sperm density observedfollowing exposure to either100mg,200mg or400mg TOCP/kg/day for14d (P＜0.05).3. Immunohistochemisty showed that NTE was expressed in mice testis,especially in the spermatogenic cells of seminiferous tubule, including spermatog-onial stem cells, spermatocytes, spermatids and sperm.4. TOCP inhibited NTEactivity in the testis in a dose-dependent manner (P<0.05), while not the mRNA levelof NTE (P>0.05).Conclusions:1. TOCP inhibits the weight coefficient of testis while not epididymis coefficient.2. TOCP could disrupt the seminiferous epithelium in thetestis and decreased the sperm density in the cauda epididymal in a dose-dependentmanner.3. NTE was shown to exist in the mice testis.4. TOCP could significantlyinhibit NTE activity in the mice testis, while not the level of NTE mRNA.