Di-(2-ethylhexyl) phthalate (diethylhexyl phthalate, DEHP) can cause male reproductive damage in rodents and human. Moreover, DEHP is known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. The PI3K/Akt/mTOR signaling pathway has been implicated in germ cell survival following testicular damage. In this study, a F0 gestation DEHP exposure and transgenerational inheritance testis injury model was established to study the testis injury phenotype and the expression and activation of members of PI3K/Akt/mTOR signaling pathway in the testis of F1–F3 generation mice. We found that the bodyweight and the anogenital distance (AGD) are reduced only in F1 mice, the sperm motility and deformity decreased in F1–F3 mice, and the testicular histomorphology damagedin F1–F3 mice; however the sperm motility and deformity rates are increased and the histomorphological injury is repaired during the transgenerational process. We also found the activation of PI3K/Akt/mTOR signaling pathway is enhanced in F1 and F2, and the number of apoptotic cells is decreased in F3 generation mice compared to the control group. These results suggest that the PI3K/Akt/mTOR signaling pathway may be activated to promote the proliferation and differentiation and protect testicular cells from apoptosis in the F1 and F2 generation mice after direct exposure to DEHP.

邻苯二甲酸二（2-乙基己基）酯（DEHP）可能对啮齿动物和人类造成雄性生殖损害。而且，已知DEHP在胎儿性腺发育期间母体暴露后可促进后代的成年疾病的跨代遗传。PI3K / Akt / mTOR信号转导通路与睾丸损伤后生殖细胞的存活有关。在这项研究中，建立了F0妊娠DEHP暴露和跨代遗传睾丸损伤模型，以研究F1-F3代小鼠睾丸损伤表型以及PI3K / Akt / mTOR信号通路成员的表达和激活。我们发现，只有F1小鼠的体重和肛门生殖器距离（AGD）降低，F1-F3小鼠的精子运动力和畸形降低，F1-F3小鼠睾丸组织形态受损；然而，在子代的过程中，精子的活力和畸形率增加了，组织形态学的损伤得以修复。我们还发现，与对照组相比，F1和F2中PI3K / Akt / mTOR信号通路的激活得到增强，而F3代小鼠中凋亡细胞的数量减少。这些结果表明，直接暴露于DEHP后，PI3K / Akt / mTOR信号通路可能被激活，以促进F1和F2代小鼠的增殖和分化并保护睾丸细胞免于凋亡。我们还发现，与对照组相比，F1和F2中PI3K / Akt / mTOR信号通路的激活得到增强，而F3代小鼠中凋亡细胞的数量减少。这些结果表明，直接暴露于DEHP后，PI3K / Akt / mTOR信号通路可能被激活，以促进F1和F2代小鼠的增殖和分化并保护睾丸细胞免于凋亡。我们还发现，与对照组相比，F1和F2中PI3K / Akt / mTOR信号通路的激活得到增强，而F3代小鼠中凋亡细胞的数量减少。这些结果表明，直接暴露于DEHP后，PI3K / Akt / mTOR信号通路可能被激活，以促进F1和F2代小鼠的增殖和分化并保护睾丸细胞免于凋亡。