Guo Jing, Lu Wen-Fa, Liang Shuang, Choi Jeong-Woo, Kim Nam-Hyung, Cui Xiang-Shun
Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju, 361-763, Republic of Korea.
College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China.
Theriogenology. 2017 Mar 1;90:266-275. doi: 10.1016/j.theriogenology.2016.11.018. Epub 2016 Nov 22.
Peroxisome proliferator-activated receptor δ (Pparδ) is a nuclear receptor that plays critical roles in lipid metabolism, glucose metabolism, and cell growth and differentiation. Several recent studies have shown that Pparδ promotes blastocyst hatching in vitro. However, the mechanism by which it promotes preimplantation embryonic development in vitro remains unclear. In this study, oocytes and parthenotes were treated with a specific agonist of PPARδ, GW501516. The activation of PPARδ had no effect on oocyte maturation for 1 μM and 10 μM GW501516 compared with the control group. Additionally, the PPARδ agonist did not affect blastocyst formation (77.79 ± 3.59% [10 μM], 79.00 ± 5.53% [50 μM], and 79.64 ± 6.00% [100 μM] vs. 81.69 ± 2.61% [control]). However, the blastocyst hatching rate was significantly greater for parthenotes treated with 10 and 50 μM agonist, and did not differ between those treated with 100 μM agonist and the control group (61.80 ± 3.03% [10 μM], 65.10 ± 5.25% [50 μM], and 38.85 ± 7.45% [100 μM] vs. 41.77 ± 10.88% [0 μM]). Activation of PPARδ also increased blastocyst quality and cell number, as well as ATP production. There were no clear differences in mitochondrial membrane potential, mitochondrion copy number, or glucose consumption between the treatment and control groups. However, PPARδ activation enhanced lipid accumulation via Fabp3 and Fabp5. Fatty acid oxidation also increased in response to treatment with the agonist via the rate-limiting gene Cpt2. Reactive oxygen species were modified and REDOX maintenance-related gene expression increased significantly in GW501516-exposed blastocysts. In addition, the activation of PPARδ resulted in changes in miRNA content. After treatment with the PPARδ agonist, miR-99 increased and miR-32 decreased. These data showed that PPARδ has a positive impact on blastocyst hatching via the regulation of lipid metabolism.
过氧化物酶体增殖物激活受体δ（Pparδ）是一种核受体，在脂质代谢、葡萄糖代谢以及细胞生长和分化中发挥关键作用。最近的几项研究表明，Pparδ可促进体外囊胚孵化。然而，其促进体外着床前胚胎发育的机制仍不清楚。在本研究中，用PPARδ的特异性激动剂GW501516处理卵母细胞和孤雌胚胎。与对照组相比，1μM和10μM的GW501516激活PPARδ对卵母细胞成熟没有影响。此外，PPARδ激动剂不影响囊胚形成（10μM时为77.79±3.59%，50μM时为79.00±5.53%，100μM时为79.64±6.00%，而对照组为81.69±2.61%）。然而，用10μM和50μM激动剂处理的孤雌胚胎的囊胚孵化率显著更高，而用100μM激动剂处理的胚胎与对照组之间没有差异（10μM时为61.80±3.03%，50μM时为65.10±5.25%，100μM时为38.85±7.45%，而0μM时为41.77±10.88%）。PPARδ的激活还提高了囊胚质量、细胞数量以及ATP产量。处理组和对照组之间在线粒体膜电位、线粒体拷贝数或葡萄糖消耗方面没有明显差异。然而，PPARδ激活通过Fabp3和Fabp5增强了脂质积累。通过限速基因Cpt2对激动剂的处理也使脂肪酸氧化增加。在暴露于GW501516的囊胚中，活性氧被修饰，与氧化还原维持相关的基因表达显著增加。此外，PPARδ的激活导致miRNA含量发生变化。用PPARδ激动剂处理后，miR-99增加，miR-32减少。这些数据表明，PPARδ通过调节脂质代谢对囊胚孵化产生积极影响。
