title: Involvement of neuropathy target esterase in tri-ortho-cresyl phosphate-induced testicular spermatogenesis failure and growth inhibition of spermatogonial stem cells in mice.
abstract: Tri-ortho-cresyl phosphate (TOCP) has been widely used in industry and reported to induce delayed neurotoxicity in humans and animals. In addition, it is known to have a deleterious effect on the male reproductive system in animals, but the precise mechanism is yet to be elucidated. The present study shows that TOCP could disrupt the seminiferous epithelium in the mouse testis and decrease the sperm density in the epididymis in a dose-dependent manner. Neuropathy target esterase (NTE) was shown to exist in mouse spermatogenic cells, including spermatogonial stem cells and to be significantly inhibited by TOCP. Likewise, saligenin cyclic-o-tolyl phosphate (SCOTP), an activated metabolite of TOCP, markedly inhibited NTE activity in spermatogonial stem cells. Both inhibition of NTE activity by SCOTP and knockdown of NTE by shRNA remarkably inhibited cell proliferation. These results point to a role of NTE in regulating proliferation of mouse spermatogonial stem cells and provide a novel insight into the mechanism by which TOCP diminishes on the sperm number in the mouse testis.
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Nanchang 330006, PR China.
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Lin-Lin
authors.initials: LL
authors.lastname: Xu
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Mei
authors.forename: Xu-Bo
authors.initials: XB
authors.lastname: Yu
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Kuang
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Liu
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002265:Carboxylic Ester Hydrolases / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D013091:Spermatogenesis / Q000187:drug effects*; D013093:Spermatogonia / Q000187:drug effects* / Q000254:growth & development; D013234:Stem Cells / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D014317:Tritolyl Phosphates / Q000494:pharmacology*
chemical_list: D014317:Tritolyl Phosphates; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; C025541:tri-o-cresyl phosphate