FGR是严重危害胎儿后天发育及健康的围产期并发症，滋养细胞外泌体中PPARγ活性降低是其主要病因学机制之一，但滋养细胞外泌体分选装载PPARγ的具体机制尚不明确。COPI蛋白复合物形成的衣被小泡是重要的蛋白质胞内运输囊泡，课题组前期研究发现COPI复合物的β亚基（COPB）与PPARγ存在直接相互作用；此外，FGR胎盘组织中泛素化修饰的PPARγ水平及其外泌体中磷酸化修饰的PPARγ占比均显著升高。由此推测COPI可能参与了滋养细胞外泌体对PPARγ的分选装载，且这一过程可能与PPARγ的翻译后修饰有关。本课题拟深入探讨滋养细胞PPARγ经COPI介导分选装载进入外泌体的机制及其与PPARγ磷酸化及泛素化修饰之间的关系，以期阐明FGR胎盘滋养细胞外泌体中PPARγ活性降低的原因，为FGR的预防及治疗提供新的研究靶点及理论基础。

Fetal growth restriction (FGR) is a perinatal complication which is growth-threatening to fetuses and newborns. Compromised activity of peroxisome proliferator-activated receptor (PPAR) γ in trophoblast exosome is considered a major cause of FGR in our group work. Till now, the specific sorting and loading mechanism of PPARγ in trophoblast exosome remains elusive. Previous studies shown that coat protein complex I (COPI)-coated vesicles are crucial intracellular protein transporter and our completed work has confirmed a direct interaction between β subunit of COPI complex and PPARγ. In addition, significantly increased ubiquitinated PPARγ in FGR placenta tissues and phosphorylated PPARγ in FGR placenta derived exosome were also observed. Based on aforementioned results we speculated that COPI complex may mediate the sorting and loading of PPARγ in trophoblast exosomes and this process is most probably affected by PPARγ phosphorylation and ubiquitination. Our present work is designed to study the PPARγ in trophoblast exosomes and PPARγ phosphorylation and ubiquitination as well as the specific sorting and loading mechanism of PPARγ in trophoblast exosomes through COPI complex. The molecular association between COPI complex mediated sorting and loading of PPARγ in trophoblast exosome and PPARγ phosphorylation and ubiquitination is designed to be investigated by point mutation in trophoblast cell model and mouse model which will be constructed by CRISPR-CAS9 genome-editing technique. Collectively, the aim of this study is to disclose the sorting and loading mechanism involved in PPARγ in trophoblast exosomes and to further provide a new research target for the prevention and treatment of FGR through modulating PPARγ sorting and loading in placenta trophoblasts.