Department of Veterinary Anatomy, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Reproduction. 2010 Feb;139(2):427-37. doi: 10.1530/REP-09-0226. Epub 2009 Nov 10.
Although di(n-butyl) phthalate (DBP), a suspected endocrine disruptor, induces testicular atrophy in prepubertal male rats, whether it exerts estrogenic activity in vivo remains a matter of debate. In the present study, we explored the estrogenic potency of DBP using 3-week-old male rats, and then examined the relationship between estrogen-induced spermatogenic cell apoptosis and testicular steroidogenesis. Daily exposure to DBP for 7 days caused testicular atrophy due to loss of spermatogenic cells, whereas testicular steroidogenesis was almost the same with the control values. A single exposure of DBP decreased testicular steroidogenesis in addition to decreasing the level of serum LH at 3 h after DBP treatment, with an extremely high incidence of apoptotic spermatogenic cells at 6 h after administration. To elucidate the estrogenic activity of DBP, we carried out an inhibition study using pure antiestrogen ICI 182,780 (ICI) in a model of spermatogenic cell apoptosis induced by DBP or estradial-3-benzoate (EB). Although both the DBP- and EB-treated groups showed a significant increase in spermatogenic cell apoptosis, ICI pretreatment significantly decreased the number of apoptotic spermatogenic cells in these two groups. In contrast, testicular steroidogenesis and serum FSH were significantly reduced in all the treated groups, even in the DBP+ICI and EB+ICI groups. Taken together, these findings led us to conclude that estrogenic compounds such as DBP and EB induce spermatogenic cell apoptosis in prepubertal rats, probably by activating estrogen receptors in testis, and that reduction in testicular steroidogenic function induced by estrogenic compounds is not associated with spermatogenic cell apoptosis.
尽管邻苯二甲酸二丁酯（DBP）是一种可疑的内分泌干扰物，会导致青春期前雄性大鼠睾丸萎缩，但它是否具有体内雌激素活性仍存在争议。在本研究中，我们使用 3 周龄雄性大鼠探讨了 DBP 的雌激素活性，然后研究了雌激素诱导的生精细胞凋亡与睾丸类固醇生成之间的关系。DBP 连续 7 天暴露导致生精细胞丢失，引起睾丸萎缩，而睾丸类固醇生成与对照组几乎相同。DBP 单次暴露除了在 DBP 处理后 3 小时降低血清 LH 水平外，还降低了睾丸类固醇生成，给药后 6 小时生精细胞凋亡的发生率极高。为了阐明 DBP 的雌激素活性，我们在 DBP 或雌二醇-3-苯甲酸（EB）诱导的生精细胞凋亡模型中使用纯抗雌激素 ICI 182,780（ICI）进行了抑制研究。尽管 DBP 和 EB 处理组的生精细胞凋亡均显著增加，但 ICI 预处理显著降低了这两组的凋亡生精细胞数量。相比之下，所有处理组的睾丸类固醇生成和血清 FSH 均显著降低，即使在 DBP+ICI 和 EB+ICI 组也是如此。总之，这些发现使我们得出结论，雌激素化合物如 DBP 和 EB 可诱导青春期前大鼠生精细胞凋亡，可能是通过激活睾丸中的雌激素受体，而雌激素化合物诱导的睾丸类固醇生成功能降低与生精细胞凋亡无关。
