Motohashi Masaya, Wempe Michael F, Mutou Tomoko, Takahashi Hiroyuki, Kansaku Norio, Ikegami Masahiro, Inomata Tomo, Asari Masao, Wakui Shin
Department of Toxicology, Laboratory Animal Science, Veterinary Anatomy, Animal Breeding, and Genetics, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Reprod Toxicol. 2016 Jan;59:139-46. doi: 10.1016/j.reprotox.2015.12.001. Epub 2015 Dec 17.
This study investigated the age-related (i.e., weeks 5, 7, 9, 14 and 17) morphological changes of Leydig cell smooth endoplasmic reticulum (LCs-ER) and testicular testosterone biosynthesis/protein expression in rats in utero exposed to di(n-butyl) phthalate (DBP) (intragastrically; 100mg/kg/day) on days 12-21 post-conception. Ultrastructural observations revealed the LCs-ER of the DBP group were non-dilated until peri-puberty, and thereafter decreased and disappeared. RT-PCR and Western blotting analyses revealed that StAR and P450scc levels in the DBP group were significantly lower at 5 and 7 weeks compared with the vehicle group but became similar during weeks 9-17. Although 3β-HSD, P450c17, and 17β-HSD levels of mRNA and protein in the DBP group were similar to the vehicle control group at 5 and 7 weeks of age, they were significantly lower during weeks 9-17. In utero DBP exposure results in age-related LCs-ER changes corresponding to reduction of testicular testosterone biosynthesis enzymes/associated proteins.
本研究调查了孕期第12至21天经口给予邻苯二甲酸二丁酯(DBP,100mg/kg/天)的大鼠中,与年龄相关的(即第5、7、9、14和17周)睾丸间质细胞滑面内质网(LCs-ER)的形态变化以及睾丸睾酮生物合成/蛋白表达情况。超微结构观察显示,DBP组的LCs-ER在青春期前未扩张,此后减少并消失。逆转录-聚合酶链反应(RT-PCR)和蛋白质免疫印迹分析显示,与溶剂对照组相比,DBP组在第5和7周时类固醇生成急性调节蛋白(StAR)和细胞色素P450侧链裂解酶(P450scc)水平显著降低,但在第9至17周时变得相似。虽然DBP组在5和7周龄时3β-羟基类固醇脱氢酶(3β-HSD)、细胞色素P450c17和17β-羟基类固醇脱氢酶(17β-HSD)的mRNA和蛋白水平与溶剂对照组相似,但在第9至17周时显著降低。孕期暴露于DBP会导致与年龄相关的LCs-ER变化,这与睾丸睾酮生物合成酶/相关蛋白的减少相对应。