College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, 250014, China.
College of Life Sciences, Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, Shandong Normal University, Jinan, Shandong, 250014, China.
Exp Cell Res. 2020 Sep 15;394(2):112151. doi: 10.1016/j.yexcr.2020.112151. Epub 2020 Jun 23.
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）可导致啮齿动物和人类雄性生殖损伤。此外，已知 DEHP 可促进母体在胎儿性腺发育期间暴露后，后代发生成年发病的跨代遗传。PI3K/Akt/mTOR 信号通路已被牵涉到睾丸损伤后生殖细胞的存活中。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，以研究睾丸损伤表型以及 PI3K/Akt/mTOR 信号通路成员在 F1-F3 代小鼠睾丸中的表达和激活。我们发现，只有 F1 代小鼠的体重和肛殖距（AGD）降低，F1-F3 代小鼠的精子活力和畸形率降低，F1-F3 代小鼠的睾丸组织形态学受损；然而，在跨代过程中，精子活力和畸形率增加，组织形态学损伤得到修复。我们还发现，PI3K/Akt/mTOR 信号通路的激活在 F1 和 F2 代增强，与对照组相比，F3 代小鼠的凋亡细胞数量减少。这些结果表明，PI3K/Akt/mTOR 信号通路可能被激活，以促进增殖和分化，并保护 F1 和 F2 代小鼠睾丸细胞免受 DEHP 的直接暴露引起的凋亡。
