Hormesis describes a biphasic dose-response relationship generally characterized by a low-dose excitement and a high-dose inhibition. This phenomenon has been observed in the regulation of cell, organ, and organismic level. However, hormesis has not reported in oocytes. In this study, we observed, for the first time, hormetic responses of PIPP levels in oocytes by inhibitor of Akt1 or PKCδ. The expression of PIPP was detected by qPCR, immunofluorescent (IF), and Western Blot (WB). To observe the changes of PIPP levels, we used the inhibitors against pAkt1 (Ser473) or PKCδ, SH-6 or sotrastaurin with low and/or high-dose, treated GV oocytes and cultured for 4 h, respectively. The results showed that PIPP expression was significantly enhanced when oocytes were treated with SH-6 or sotrastaurin 10 μM, but decreased with SH-6 or sotrastaurin 100 μM. We also examined the changes of PIPP levels when GV oocytes were treated with exogenous PtdIns(3,4,5)P₃ or LY294002 for 4 h. Our results showed that PIPP level was enhanced much higher under the treatment of 0.1 μM PtdIns(3,4,5)P₃ than that of 1 μM PtdIns(3,4,5)P₃, which is consistent with the changes of PIPP when oocytes were treated with inhibitors of pAkt1 (Ser473) or PKCδ. In addition, with PIPP siRNA, we detected that down-regulated PIPP may affect distributions of Akt, Cdc25, and pCdc2 (Tyr15). Taken together, these results show that the relationships between PIPP and Akt may follow the principle of hormesis and play a key role during release of diplotene arrest in mouse oocytes.

Hormesis 描述了一种双相剂量反应关系，通常以低剂量兴奋和高剂量抑制为特征。这种现象已经在细胞、器官和有机体水平的调节中观察到。然而，尚未报道卵母细胞中的兴奋作用。在这项研究中，我们首次观察到 Akt1 或 PKCδ 抑制剂对卵母细胞中 PIPP 水平的激素反应。通过qPCR、免疫荧光（IF）和Western Blot（WB）检测PIPP的表达。为了观察 PIPP 水平的变化，我们使用针对 pAkt1 (Ser473) 或 PKCδ、SH-6 或 sotrastaurin 的抑制剂与低剂量和/或高剂量处理的 GV 卵母细胞分别培养 4 小时。结果表明，当卵母细胞用 SH-6 或 sotrastaurin 10 μM 处理时，PIPP 表达显着增强，但用 SH-6 或 sotrastaurin 100 μM 处理时降低。₃或 LY294002 4 小时。我们的结果表明，在0.1 μM PtdIns(3,4,5) P ₃处理下PIPP水平的提高远高于1 μM PtdIns(3,4,5) P ₃，这与PIPP的变化一致当卵母细胞用 pAkt1 (Ser473) 或 PKCδ 抑制剂处理时。此外，使用 PIPP siRNA，我们检测到下调的 PIPP 可能影响 Akt、Cdc25 和 pCdc2 (Tyr15) 的分布。综上所述，这些结果表明 PIPP 和 Akt 之间的关系可能遵循兴奋作用原理，并在小鼠卵母细胞释放双线烯阻滞过程中起关键作用。