Lian-Ju Shen1, Xiang-Liang Tang, Chun-Lan Long, Xi-Ning Cao, Yi Wei, Yang-Cai Wang, Mang Sun, Yue Zhou, Yang Liu, Bo Liu, Fang-Yuan Huang, Guang-Hui Wei. 1. Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders; Chongqing Key Laboratory of Pediatrics Chongqing, 400014, China.E-mail: kafei69200@126.com.
Abstract
OBJECTIVE: To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats. METHODS: Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin β-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot. RESULTS: Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and β-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05). CONCLUSIONS: DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.
OBJECTIVE: To investigate mechanism of di-(2-ethylhcxyl)phthalate (DEHP) exposure in causing blood-testis barrier (BTB) impairment in rats. METHODS: Two-months-old male SD rats were randomly divided into corn oil control group and DEHP (750 mg/kg) exposure group for daily intragastic treatment for 30 consecutive days. After the treatments the rats were examined for histomorphological changes of the testicle using HE staining and the expressions of the junction proteins N-cadherin β-catenin, occludin and connexin43 of the BTB using Western blot. In the in vitro study, the vitality and ROS generation level in Sertoli cells exposed to different concentrations of DEHP were examined with MTT and ROS assay kits, respectively, and Nrf2 and p-p38 expressions were detected with Western blot. RESULTS: Compared with the control group, the rats with DEHP exposure showed structural damage of the seminiferous tubule and polarity loss of the spermatids. DEHP exposure caused significantly decreased expressions of occludin and connexin43 but increased expressions of N-cadherin and β-catenin in the testicle tissues of the rats (P<0.05). The vitality of Sertoli cells was obviously decreased and ROS level increased significantly after exposure of the cells to increasing concentrations of DEHP, which also resulted in significantly up-regulated Nrf2 and p-p38 expressions (P<0.05). CONCLUSIONS:DEHP exposure causes increased oxidative stress in the Sertoli cells of the testis, activates p38 MAPK signaling pathway, and results eventually in impaired spermatogenesis in rats.
Authors: Manash K Paul; Bharti Bisht; Daphne O Darmawan; Richard Chiou; Vi L Ha; William D Wallace; Andrew T Chon; Ahmed E Hegab; Tristan Grogan; David A Elashoff; Jackelyn A Alva-Ornelas; Brigitte N Gomperts Journal: Cell Stem Cell Date: 2014-06-19 Impact factor: 24.633
Authors: Lauren M Tetz; Adrienne A Cheng; Cassandra S Korte; Roger W Giese; Poguang Wang; Craig Harris; John D Meeker; Rita Loch-Caruso Journal: Toxicol Appl Pharmacol Date: 2013-01-27 Impact factor: 4.219
Authors: Xiang Xiao; Dolores D Mruk; Elizabeth I Tang; Chris K C Wong; Will M Lee; Constance M John; Paul J Turek; Bruno Silvestrini; C Yan Cheng Journal: Hum Reprod Date: 2014-02-13 Impact factor: 6.918