Resveratrol-Loaded PLGA Enhanced Vitrified Oocyte Viability through Rab11fip4/Arf5-Mediated Internalization Route
文献类型： 外文期刊
作者： Zhu, Yixiao 1 ; Li, Jun 2 ; Zhou, Guizhen 1 ; Zou, Xinhua 1 ; Liu, Aiju 1 ; ReYiMuJiang, YiZaiTiGuLi 1 ; Sun, Yidan 3 ; Luo, Yuwen 3 ; Xia, Hongze 3 ; Bai, Jiachen 1 ; Liu, Hejie 1 ; Hou, Yunpeng 3 ; Fu, Xiangwei 1 ;
作者机构： 1.China Agr Univ, Coll Anim Sci & Technol,Natl Engn Lab Anim Breedin, State Key Lab Anim Biotech Breeding, Key Lab Anim Genet Breeding & Reprod MARA, Beijing 100193, Peoples R China
2.Hebei Med Univ, Hosp 1, Reprod Med Ctr, Dept Reprod Med, Shijiazhuang 050000, Peoples R China
3.China Agr Univ, Coll Biol Sci, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China
4.Xinjiang Acad Agr & Reclamat Sci, Inst Anim Husb & Vet Sci, State Key Lab Sheep Genet Improvement & Hlth Breed, Shihezi 832000, Peoples R China
关键词： Rab11fip4; nanoparticles; endocytosis; vitrification; oocytes
期刊名称：ACS APPLIED MATERIALS & INTERFACES （ 影响因子：8.2； 五年影响因子：8.5 ）
ISSN： 1944-8244
年卷期： 2025 年 17 卷 31 期
页码：
收录情况： SCI
摘要： Irreversible injury accompanied by oocyte vitrification is still challenging. Recent advances in nanotechnology offer promising therapeutic potential. However, the molecular mechanisms by which nanomaterials protect vitrified oocytes remain elusive. In this study, resveratrol-loaded poly(lactic-co-glycolic acid) nanoparticles (PLGA-RES) were synthesized, and the successful synthesis was confirmed by the results of Fourier transform infrared spectroscopy (FTIR) characterization. Thereafter, the effect of PLGA-RES on the quality of vitrified oocytes was explored. Our results showed that the synthesized PLGA-RES nanoparticles, with an average size of 163.5 nm, demonstrated time- and dose-dependent internalization in mouse oocytes. Transmission electron microscopy (TEM) analysis revealed their distribution around the membrane and perinuclear region. Treatment with PLGA-RES significantly increased the germinal vesicle breakdown (GVBD) rate and reduced the aneuploidy rate in vitrified oocytes. Transcriptome analysis identified 447 upregulated and 185 downregulated mRNAs, with the endocytosis pathway playing a crucial role in PLGA-RES regulation. Short time-series expression miner analysis (STEM) and weighted gene coexpression network analysis (WGCNA) further identified Rab11fip4 as a core gene in the PLGA-RES internalization, which was also confirmed by a molecular docking study. Rab11fip4 was further found to interact with Arf5 via coimmunoprecipitation (co-IP) analysis. Knockdown of Rab11fip4 significantly impaired oocyte maturation and nanoparticles internalization. Further experiments showed that the internalization of PLGA-RES was decreased by endocytic inhibitors, and the Rab11fip4-mediated recycling endosome pathway could protect PLGA-RES from lysosomal degradation. In summary, PLGA-RES could improve vitrified oocyte viability through the endocytic pathway, highlighting the importance of Rab11fip4 in nanoparticle internalization and functional modulation.
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