Martino-Andrade Anderson J, Morais Rosana N, Botelho Giuliana G K, Muller Graziela, Grande Simone W, Carpentieri Giovanna B, Leão Gabriel M C, Dalsenter Paulo R
Departamento de Fisiologia, Centro Politécnico, Universidade Federal do Paraná, Setor de Ciências Biológicas, Curitiba, Brazil.
Int J Androl. 2009 Dec;32(6):704-12. doi: 10.1111/j.1365-2605.2008.00939.x. Epub 2008 Dec 16.
The reproductive effects of the coadministration of di-2-(ethylhexyl) phthalate (DEHP) and di-butyl phthalate (DBP) were studied in both foetal and adult male rat offspring exposed in utero. Pregnant Wistar rats were treated by oral gavage from gestation day 13 to 21 with vehicle control, 150 mg DEHP/kg body weight (bw)/day, 100 mg DBP/kg bw/ or a combination of the two compounds (DEHP 150 + DBP 100 mg/kg bw/day). An additional group of dams received 500 mg DBP/kg bw/day. A significant decrease in foetal testicular testosterone levels was observed in animals exposed to 500 mg DBP/kg/day or the phthalate mixture. Similarly, histological analysis of the foetal testis revealed that the coadministration of DEHP and DBP was able to increase the diameter of seminiferous cords and induce gonocyte multinucleation at doses that individually had no significant effects on these variables. However, in the phthalate mixture group, no significant changes were observed in anogenital distance and nipple retention, variables that are used to indicate possible anti-androgenic effects. Also, the adult endpoints investigated, that included reproductive organ weights and the number of spermatids per testis, were unaffected by any treatment regimen. Overall, coadministration of DEHP and DBP in utero significantly reduced testicular testosterone levels and resulted in misshapen seminiferous cords and gonocyte multinucleation in rat foetal testis. Our results also confirm that these foetal endpoints seem to be the most sensitive markers of prenatal phthalate exposure.
研究了在子宫内暴露的胎儿和成年雄性大鼠后代中，邻苯二甲酸二（2-乙基己基）酯（DEHP）和邻苯二甲酸二丁酯（DBP）共同给药的生殖影响。从妊娠第13天至21天，对怀孕的Wistar大鼠进行灌胃处理，分别给予溶剂对照、150 mg DEHP/千克体重（bw）/天、100 mg DBP/千克bw/天或两种化合物的组合（DEHP 150 + DBP 100 mg/千克bw/天）。另一组母鼠接受500 mg DBP/千克bw/天的剂量。在暴露于500 mg DBP/千克/天或邻苯二甲酸酯混合物的动物中，观察到胎儿睾丸睾酮水平显著降低。同样，胎儿睾丸的组织学分析表明，DEHP和DBP共同给药能够增加生精索的直径，并在单独对这些变量无显著影响的剂量下诱导生殖母细胞多核化。然而，在邻苯二甲酸酯混合物组中，用于指示可能的抗雄激素作用的肛门生殖器距离和乳头保留方面未观察到显著变化。此外，所研究的成年终点，包括生殖器官重量和每个睾丸的精子细胞数量，均未受到任何治疗方案的影响。总体而言，子宫内DEHP和DBP共同给药显著降低了睾丸睾酮水平，并导致大鼠胎儿睾丸中生精索畸形和生殖母细胞多核化。我们的结果还证实，这些胎儿终点似乎是产前邻苯二甲酸酯暴露最敏感的标志物。
