School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Biol Reprod. 2013 May 2;88(5):112. doi: 10.1095/biolreprod.112.106104. Print 2013 May.
Recent evidence has linked human phthalate exposure to abnormal reproductive and hormonal effects. Phthalates are plasticizers that confer flexibility and transparency to plastics, but they readily contaminate the body and the environment. In this study, timed pregnant CD1 outbred mice were treated with di-(2-ethylhexyl) phthalate (DEHP) from Embryonic Day 7 (E7) to E14. The subsequent generation (F1) offspring were then bred to produce the F2, F3, and F4 offspring, without any further DEHP treatment. This exposure scheme disrupted testicular germ cell association and decreased sperm count and motility in F1 to F4 offspring. By spermatogonial transplantation techniques, the exposure scheme also disrupted spermatogonial stem cell (SSC) function of F3 offspring. The W/W(V) recipient testes transplanted with F3 offspring germ cells from the DEHP-treated group had a dramatically lower percentage of donor germ cell-derived spermatogenic recovery in seminiferous tubules when compared to the recipient testes transplanted with CD1 control germ cells. Further characterization showed that the major block of donor germ cell-derived spermatogenesis was before the appearance of undifferentiated spermatogonia. Interestingly, the testes transplanted with the F3 offspring germ cells from the DEHP-treated group, when regenerated, replicated testis morphology similar to that observed in the testes from the F1 to F3 offspring of the DEHP-treated group, suggesting that the germ cell disorganization phenotype originates from the stem cells of F3 offspring. In conclusion, embryonic exposure to DEHP was found to disrupt testicular germ cell organization and SSC function in a transgenerational manner.
最近的证据表明，人类邻苯二甲酸酯暴露与生殖和激素异常有关。邻苯二甲酸酯是一种增塑剂，能使塑料具有柔韧性和透明度，但它们很容易污染人体和环境。在这项研究中，用邻苯二甲酸二（2-乙基己基）酯（DEHP）处理从胚胎第 7 天（E7）到第 14 天的 CD1 近交系怀孕小鼠。随后的 F1 代后代被繁殖产生 F2、F3 和 F4 代后代，没有进一步的 DEHP 处理。这种暴露方案打乱了睾丸生殖细胞的联系，并减少了 F1 到 F4 代后代的精子数量和活力。通过精原干细胞移植技术，暴露方案还扰乱了 F3 代后代的精原干细胞（SSC）功能。与接受来自 DEHP 处理组的 CD1 对照生殖细胞的受体睾丸相比，接受来自 DEHP 处理组的 F3 代后代生殖细胞的 W/W(V)受体睾丸在生精小管中供体生殖细胞衍生的精子发生恢复的百分比明显较低。进一步的特征表明，供体生殖细胞衍生的精子发生的主要障碍发生在未分化精原细胞出现之前。有趣的是，从 DEHP 处理组的 F3 代后代生殖细胞移植的睾丸在再生时，复制的睾丸形态与 DEHP 处理组的 F1 到 F3 代后代的睾丸相似，这表明生殖细胞组织紊乱表型来源于 F3 代后代的干细胞。总之，胚胎暴露于 DEHP 被发现以跨代的方式破坏睾丸生殖细胞组织和 SSC 功能。
