Wilson Vickie S, Howdeshell Kembra L, Lambright Christy S, Furr Johnathan, Earl Gray L
U.S. Environmental Protection Agency, ORD, NHEERL, Reproductive Toxicology Division, MD-72, Research Triangle Park, NC 27711, USA.
Toxicol Lett. 2007 May 15;170(3):177-84. doi: 10.1016/j.toxlet.2007.03.004. Epub 2007 Mar 14.
Exposure to phthalate esters during sexual differentiation disrupts testosterone and insulin-like three hormones resulting in malformations of androgen- and insulin-like three-dependent tissues. The current study was designed to test the hypothesis that gubernacular lesions would be more prevalent in the DEHP-treated (750 mg/kg/day, gestational days 14-18) Wistar male than in the SD rat offspring, whereas the SD rat would display a higher incidence of epididymal agenesis. As hypothesized, striking differences were seen in the incidences of epididymal (67% in SD versus 8% in Wistar) and gubernacular lesions (0% in SD versus 64% in Wistar) among the two strains. In addition, fetal androgen and insl3 mRNA levels differed among the strains. SD fetal males had higher insl3 mRNA and lower T levels than Wistar males. The ratio of insl3 mRNA to T differed among DEHP-treated SD and Wistar fetal males, indicating that the steroidogenic pathway was more affected in the SD strain than in the Wistar strain. Taken together, these results suggest that the different malformation profiles produced by in utero phthalate treatment arise, at least in part, from strain differences in fetal Leydig cell function and the manner in which these cells respond to DEHP treatment.
在性别分化期间接触邻苯二甲酸酯会干扰睾酮和胰岛素样 3 激素,导致雄激素和胰岛素样 3 依赖性组织出现畸形。本研究旨在验证以下假设:在经邻苯二甲酸二(2-乙基己基)酯(DEHP)处理(750 毫克/千克/天,妊娠第 14 - 18 天)的 Wistar 雄性大鼠后代中,睾丸引带损伤比 SD 大鼠后代更普遍,而 SD 大鼠附睾发育不全的发生率更高。正如所假设的那样,在两个品系中,附睾损伤发生率(SD 为 67%,Wistar 为 8%)和睾丸引带损伤发生率(SD 为 0%,Wistar 为 64%)存在显著差异。此外,品系间胎儿雄激素和胰岛素样 3 基因(insl3)mRNA 水平也有所不同。SD 胎儿雄性比 Wistar 胎儿雄性具有更高的 insl3 mRNA 水平和更低的睾酮(T)水平。经 DEHP 处理的 SD 和 Wistar 胎儿雄性之间 insl3 mRNA 与 T 的比值不同,这表明在 SD 品系中类固醇生成途径比 Wistar 品系受影响更大。综上所述,这些结果表明,子宫内邻苯二甲酸酯处理产生的不同畸形特征至少部分源于胎儿睾丸间质细胞功能的品系差异以及这些细胞对 DEHP 处理的反应方式。