Xiang Han, Wang Shao, Kong Xiaoyan, Yu Yihang, Shen Lianju, Long Chunlan, Liu Xing, Wei Guang-Hui
Department of Urology; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Key Laboratory of Child Urogenital Development and Tissue Engineering; Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.
Syst Biol Reprod Med. 2021 Jun;67(3):193-200. doi: 10.1080/19396368.2020.1862356. Epub 2021 Feb 22.
This study aimed to investigate the expression of Fos proto-oncogene, AP-1 transcription factor subunit (c-Fos) in the genital tubercle (GT) of rats with di(2-ethylhexyl) phthalate (DEHP)-induced hypospadias and in the prepuce of patients with hypospadias compared with unaffected controls. Pregnant rats were given 750 mg/kg/day DEHP orally from gestational days 12-19. Western blotting showed that c-Fos expression was increased in DEHP-induced hypospadiac male offspring. In addition, 30 prepuce tissue specimens obtained during hypospadias repair surgery were divided into 2 groups: the mild hypospadias group (n = 15) and the severe hypospadias group (n = 15). Fifteen normal prepuce tissue specimens were harvested during elective circumcision as normal controls. Real-time quantitative polymerase chain reaction, western blotting and immunohistochemistry analyses were used to assess c-Fos expression. c-Fos protein levels were higher in the GT of DEHP-induced rats than in that of control rats. c-Fos mRNA and protein levels were also higher in the hypospadias groups than in the control group ( < 0.05, < 0.001), and c-Fos protein levels were significantly higher in the severe hypospadias group than in the mild hypospadias group ( < 0.01). The expression of c-Fos was increased in both the GT of DEHP-induced hypospadiac rats and the prepuce of hypospadias patients. Thus, c-Fos overexpression might contribute to hypospadias. DEHP: di(2-ethylhexyl) phthalate; c-Fos: Fos proto-oncogene, AP-1 transcription factor subunit; Mafb: the masculinization-regulatory gene v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B; GT: genital tubercle; ED: embryonic day; AGD: anogenital distance; AGI: anogenital distance index; ED: embryonic day.
本研究旨在调查邻苯二甲酸二（2-乙基己基）酯（DEHP）诱导的尿道下裂大鼠生殖结节（GT）以及尿道下裂患者包皮中Fos原癌基因、AP-1转录因子亚基（c-Fos）的表达，并与未受影响的对照组进行比较。妊娠大鼠在妊娠第12至19天经口给予750 mg/kg/天的DEHP。蛋白质印迹法显示，在DEHP诱导的尿道下裂雄性后代中，c-Fos表达增加。此外，将尿道下裂修复手术中获取的30份包皮组织标本分为2组：轻度尿道下裂组（n = 15）和重度尿道下裂组（n = 15）。在择期包皮环切术中获取15份正常包皮组织标本作为正常对照。采用实时定量聚合酶链反应、蛋白质印迹法和免疫组织化学分析来评估c-Fos的表达。DEHP诱导的大鼠GT中c-Fos蛋白水平高于对照大鼠。尿道下裂组的c-Fos mRNA和蛋白水平也高于对照组（P<0.05，P<0.001），且重度尿道下裂组的c-Fos蛋白水平显著高于轻度尿道下裂组（P<0.01）。DEHP诱导的尿道下裂大鼠的GT和尿道下裂患者的包皮中c-Fos表达均增加。因此，c-Fos过表达可能与尿道下裂有关。DEHP：邻苯二甲酸二（2-乙基己基）酯；c-Fos：Fos原癌基因、AP-1转录因子亚基；Mafb：雄性化调节基因v-maf肌腱膜纤维肉瘤癌基因家族蛋白B；GT：生殖结节；ED：胚胎日；AGD：肛殖距；AGI：肛殖距指数；ED：胚胎日
