臺灣博碩士論文加值系統

隨著年齡增長以及生活環境型態等因素，使婦女發生不孕症比例年年增加。輸卵管在生殖系統中扮演重要的角色，不只是精子卵子結合的地方更是能幫助早期胚發育，而輸卵管細胞所分泌細胞外囊泡（extracellular vesicles, EVs）包含脂質、蛋白質、核醣核酸和短片段核醣核酸（microRNAs, miRNAs）等生物調控因子，推測可以幫助細胞與細胞之間的交互作用促進卵母細胞的受精及發育。目前豬輸卵管細胞對於卵母細胞之研究甚少，並且無深入探討輸卵管分泌EVs之成分。故擬探討豬輸卵管幹細胞（Porcine fallopian tube stem cells, PFTSCs）所分泌之細胞外囊泡對於卵母細胞之影響，並鑑定PFTSCs中的EVs並分析高表現之miRNAs，期望找出促進豬胚發育之因子。因此將PFTSCs培養至第五代，待細胞密度達80~90%時，換成豬體外成熟培養液（M199）培養3小時，再將其條件培養液（condition medium, CM）培養卵母細胞，發現卵母細胞成熟率顯著提升。為定義CM中EVs，以沉降法的方式收集EVs。先檢測肌動蛋白（β-actin）、熱休克蛋白（heat shock proteins 70, HSP70）及細胞色素c（cytochrome c, CYT C）等蛋白質的存在狀態以確認EVs無細胞參雜。同時使用超高解析度熱場發射掃描式電子顯微鏡（Field Emission Scanning Electron Microscope, FE-SEM）和奈米粒子追蹤分析儀來觀察及定義EVs型態。再利用NGS分析EVs並檢測出267種miRNAs，其中選出表現量最高的14種分析其GO（Gene Ontology）及KEGG（Kyoto Encyclopedia of Genes and Genomes）路徑富集圖。這14種miRNAs的可能功能和MAPK路徑與減數分裂有高度相關性，故我們選擇了miR-152-3p、miR-148a-3p、miR-320a-3p、let-7f-5p及miR-22-3p等五種miRNAs，皆有可能影響標的CEPB基因，而再影響MAPK路徑。五種miRNAs分別於體外成熟（IVM）添加培養後，發現添加miR-320a-3p之組別成熟率顯著最高，則後續孤雌激活豬胚之囊胚率以IVM添加50 nM的miR-320a-3p顯著最高。其餘miRNAs處理下，卵母細胞成熟率、後續孤雌激活豬胚之卵裂率、囊胚率及細胞數不受影響。於體外培養（IVC）添加miR-320a-3p組別之囊胚率顯著高於對照組，但不影響其卵裂率及細胞數。綜合之結果說明，豬輸卵管幹細胞之條件培養液能助於卵母細胞的發育，收集條件培養液中細胞外囊泡與分析，也鑑定出最有可能影響卵母細胞的miRNA為miR-320a-3p，除了不只可以幫助卵母細胞的成熟，更能有效提升囊胚率。

With the increase of age and the types of living environments and other factors, the infertility of Taiwanese women increases yearly. The fallopian tube is essential in the reproductive system, for combining sperms and eggs and helping early embryonic development. Extracellular vesicles (EVs) secreted by fallopian tube contain biological regulatory factors, such as lipids, proteins and microRNAs (miRNAs). It’s suggested that EVs can help the fertilization and development of oocytes. At present, the researches on oocytes from porcine oviduct cells are rare, and the study of the components from oviduct secreting EVs remains vague. Therefore, to explore the effect of EVs secreted by porcine fallopian tube stem cells (PFTSCs) on oocytes, to identify EVs functions in PFTSCs and to uncover potential miRNAs, are the goals to promote the porcine embryonic developments. First of all, when the fifth-generation PFTSCs were reached 80-90% confluency, cultural medium was replaced with pig in vitro maturation medium (M199) and cultured for 3 hours, and collected the condition medium (CM) for oocyte incubations. The maturation rate was significantly increased after CM incubation. To understand functions of EVs in CM, EVs were collected by sedimentation approach. Proteins as ACTIN, HSP70 (heat shock proteins 70) and CYT C (cytochrome c) were used to determine whether extracted EVs were cell-free. Field Emission Scanning Electron Microscope (FE-SEM) and Nanoparticle Tracking Analyzer were used to observe EVs morphology, with a defined particle size range from 100-200 nm. The EVs were further analyzed by NGS and identified 267 miRNAs, and the 14 with the highest expression levels were selected to analyze the GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment maps, and the results suggested that the function and MAPK pathway are highly related to meiosis. The selected miR-152-3p, miR-148a-3p, miR-320a-3p, let-7f-5p and miR-22-3p, were predicted to target Cepb1 gene, Cepb1 was also reported to affect MAPK pathway. After separately adding five miRNAs and cultured in vitro maturation, the maturation rate of the group with miR-320a-3p was significantly increased. The subsequent parthenogenetic activation of the blastocyst rate of pig embryos was also significantly enhanced by adding 50 nM miR-320a-3p. The other miRNAs shared no effects on oocyte maturations, on cleavage rates, blastocyst rates, and neither on cell numbers of subsequent parthenogenetic porcine embryos. In vitro culture with miR-320a-3p, the blastocyst rate was significantly higher than control group, and the cleavages rate and cell numbers were not affected by miR-320a-3p. The results showed that the CM of PFTSCs can effectively improve porcine oocyte development, and the miRNAs in EVs are sequenced and identified. It was found that miR-320a-3p can not only help the maturation, but also can effectively increase the blastocyst rates.

摘要 I
Abstract III
謝誌 V
目錄 VI
圖表目錄 VIII
壹、前言 1
貳、文獻回顧 3
一、 輸卵管 3
(一)、 輸卵管結構 3
(二)、 輸卵管旁分泌物 3
二、 卵母細胞成熟 4
(一)、 核成熟 5
(二)、 質成熟 5
(三)、 細胞週期基因表現 6
三、 卵母細胞激活 8
四、 細胞外囊泡 8
(一)、 細胞外囊泡的基本特性 8
(二)、 細胞外囊泡蛋白質組成 9
五、 細胞外囊泡與細胞交互作用 12
六、 短片段核糖核酸（microRNA） 13
(一)、 命名方式 13
(二)、 microRNAs基本特性 14
(三)、 濾泡液miRNAs表現 15
(四)、 卵母細胞miRNAs表現 15
參、 試驗研究 16
一、 材料方法 16
(一)、 豬卵母細胞之體外成熟培養（IVM）液配製 16
(二)、 豬輸卵管幹細胞培養液配製 16
(三)、 豬卵母細胞體外成熟培養 18
(四)、 豬卵母細胞之激活處理 18
(五)、 卵母細胞之激活處理 18
(六)、 孤雌激活豬胚之體外培養（IVC）液配製 19
(七)、 豬輸卵管幹細胞之EVs特性分析 20
(八)、 源自PFTSCs的EVs蛋白質及miRNAs種類分析。 21
(九)、 卵母細胞成熟培養所需miRNAs之製備 22
(十)、 試驗設計 22
(十一)、 統計分析 26
二、 結果與討論 27
(一)、 試驗一：不同儲存方法之PFTSCs條件培養液對體外成熟之豬卵母細胞的影響。 27
(二)、 試驗二：探討源自豬輸卵管幹細胞之EVs的特性。 29
(三)、 試驗三：檢測來自PFTSC的EVs和分析EVs中的miRNAs。 32
(四)、 試驗四：在IVM/IVC過程中添加不同濃度miRNAs觀察卵母細胞發育能力。 40
肆、 結論 48
伍、 參考文獻 50
作者簡介 67

劉康佑。2019。豬及牛隻輸卵管幹細胞旁分泌物效益對體外成熟及孤雌激活豬胚發育之探討。碩士論文，國立屏東科技大學動物科學與畜產系。屏東縣。
Abbara, A., S. A. Clarke, and W. S. Dhillo. 2018. Novel Concepts for Inducing Final Oocyte Maturation in In Vitro Fertilization Treatment. Endocr Rev. 9(5): 593-628.
Abels, E. R. and X. O. Breakefield. 2016. Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol. 36(3):301-12.
Al-Dossary, A. A., P. Bathala, J. L. Caplan, and P. A. Martin-DeLeon. 2015. Oviductosome-sperm membrane interaction in cargo delivery: detection of fusion and underlying molecular players using three-dimensional super-resolution structured illumination microscopy (SR-SIM). J Biol Chem. 290(29): 17710-17723.
Almiñana, C., E. Corbin, G. Tsikis, A.S. Alcântara-Neto, V. Labas, K. Reynaud, L. Galio, R. Uzbekov, A.S. Garanina, X. Druart and P. Mermillod. 2017. Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk. Reproduction 154: 253-268.
Ardon, F., R. D. Markello, L. Hu, Z. I. Deutsch, C. K. Tung, M. Wu, and S. S. Suarez. 2016. Dynamics of bovine sperm interaction with epithelium differ between oviductal isthmus and ampulla. Biol Reprod. 95(4): 90.
Azizi, M., L. Teimoori-Toolabi, M. K. Arzanani, K. Azadmanesh, P. Fard-Esfahani, and S. Zeinali. 2014. MicroRNA-148b and microRNA-152 reactivate tumor suppressor genes through suppression of DNA methyltransferase-1 gene in pancreatic cancer cell lines. Cancer Biol Ther. 15(4): 419-427.
Barry, O. P. and G.A. FitzGerald. 1999. Mechanisms of cellular activation by platelet microparticles. Thromb. Haemost. 82: 794-800.
Barry, O. P., D. Pratico, R. C. Savani, and G. A. FitzGerald. 1998. Modulation of monocyte–endothelial cell interactions by platelet microparticles. J. Clin. Invest. 102: 136-144.
Bathala, P., Z. Fereshteh, K. Li, A. A. Al-Dossary, D. S. Galileo, and P. A. Martin-DeLeon. 2018. Oviductal extracellular vesicles (oviductosomes, OVS) are conserved in humans: murine OVS play a pivotal role in sperm capacitation and fertility. Mol Hum Reprod. 24(3): 143-157.
Besenfelder, U., V. Havlicek, and G. Brem. 2012. Role of the oviduct in early embryo development. Reprod. Domest. Anim. 47(4): 156-163.
Bos-Mikich, A., F. F. Bressan, R. R. Ruggeri, Y. Watanabe, and F. V. Meirelles. 2016. Parthenogenesis and Human Assisted Reproduction. Stem Cells Int. 2016: 1970843.
Chen, J., C. Li, and L. Chen. 2015. The role of microvesicles derived from mesenchymal stem cells in lung diseases. Biomed Res Int. 2015: 985814.
Chen, J., C. Melton, N. Suh, J. S. Oh, K. Horner, F. Xie, C. Sette, R. Blelloch, and M. Conti. 2011. Genome-wide analysis of translation reveals a critical role for deleted in azoospermia-like (Dazl) at the oocyte-to-zygote transition. Genes Dev. 25(7): 755-766.
Chen, J., S. Torcia, F. Xie, C. J. Lin, H. Cakmak, F. Franciosi, K. Horner, C. Onodera, J. S. Song, M. I. Cedars, M. Ramalho-Santos, and M. Conti. 2013. Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes. Nat. Cell Biol. 15(12): 1415-1423.
Chen, L., J. C. Jiang, X. X. Dai, and H. Y. Fan. 2020. Function and molecular mechanism of mitogen-activated protein kinase (MAPK) in regulating oocyte meiotic maturation and ovulation. Molecular Endocrinology. 72(1): 48-62.
Conti, M. and F. Franciosi. 2018. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum Reprod 24(3): 245-266.
Conti, M., C. B. Andersen, F. J. Richard, K. Shitsukawa, and A. Tsafriri. 1998. Role of cyclic nucleotide phosphodiesterases in resumption of meiosis. Mol Cell Endocrinol. 145(1-2): 9-14.
Corbeel, L. and K. Freson. 2008. Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders. Eur J Pediatr. 167: 723-729.
Coticchio, G., E. Sereni, L. Serrao, S. Mazzone, I. Iadarola, and A. Borini. 2004. What criteria for the definition of oocyte quality? Ann N Y Acad Sci. 1034: 132-144.
Coticchio, G., M. Dal Canto, M. Mignini Renzini, M. C. Guglielmo, F. Brambillasca, D. Turchi, P. V. Novara, and R. Fadini. 2015. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Hum. Reprod. Update. 21(4): 427-454.
da Silveira, J. C., D. N. Veeramachaneni, Q. A. Winger, E. M. Carnevale, and G. J. Bouma. 2012. Cell-secreted vesicles in equine ovarian follicular fluid contain miRNAs and proteins: a possible new form of cell communication within the ovarian follicle. Biol Reprod. 86(3): 71.
Dadashpour-Davachi N., A. Zare-Shahneh, H. Kohram, M. Zhandi, H. Shamsi, A. M. Hajiyavand, and M. Saadat. 2016. Differential influence of ampullary and isthmic derived epithelial cells on zona pellucida hardening and in vitro fertilization in ovine. Reprod Biol. 16(1):61-69.
Dadashpour-Davachi N., H. Kohram, A. Zare-Shahneh, M. Zhandi, A. Goudarzi, R. Fallahi, R. Masoudi, A. R. Yousefi, and P. M. Bartlewski P. 2017. The effect of conspecific ampulla oviductal epithelial cells during in vitro maturation on oocyte developmental competence and maturation-promoting factor (MPF) activity in sheep. Theriogenology. 88:207-214.
Dadashpour-Davachi N., R. Fallahi, E. Dirandeh, X. Liu, and P. M. Bartlewski. 2018. Effects of co-incubation with conspecific ampulla oviductal epithelial cells and media composition on cryotolerance and developmental competence of in vitro matured sheep oocytes. Theriogenology. 120:10-15.
Dai, J., X. Huang, C. Zhang, X. Luo, S. Cao, J. Wang, B. Liu, and J. Gao. 2021. Berberine regulates lipid metabolism via miR-192 in porcine oocytes matured in vitro. Vet Med Sci. 7(3):950-959.
Dan Dunn, J., L. A. Alvarez, X. Zhang, and T. Soldati. 2015. Reactive oxygen species and mitochondria: a nexus of cellular homeostasis. Redox Biol. 6: 472-485.
Dashti S., A. Zare-Shahneh, H. Kohram, M. Zhandi, and N. Dadashpour -Davachi. 2016. Differential influence of ovine oviduct ampullary and isthmic derived epithelial cells on in vitro early embryo development and kinetic. Small Ruminant Research. 136:197-201.
De La Fuente, R. 2006. Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Dev Biol. 292(1): 1-12.
Ding, C., C. Qian, S. Hou, J. Lu, Q. Zou, H. Li, and B. Huang. 2020. Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to prevent reactive oxygen species generation in POI. Mol Ther Nucleic Acids. 21: 37-50.
Dionne, T., Rebecca D., A. Zahraa, and S. Jennifer. 2014. Extracellular vesicles and reproduction–promotion of successful pregnancy. Cellular & Molecular Immunology. 11: 548-563.
DiTacchio, K. A., S. F. Heinemann, and G. Dziewczapolski. 2015. Metformin treatment alters memory function in a mouse model of Alzheimer's disease. J Alzheimers Dis. 44(1): 43-48.
Du, T. and P. D. Zamore. 2005. microPrimer: the biogenesis and function of microRNA. Development. 132(21): 4645-4652.
Dziuk, P. 1985. Effect of migration, distribution and spacing of pig embryos on pregnancy and fetal survival. J Reprod Fertil Suppl. 33: 57-63.
Egbert, J. R., L. C. Shuhaibar, A. B. Edmund, D. A. Van Helden, J. W. Robinson, T. F. Uliasz, V. Baena, A. Geerts, F. Wunder, L. R. Potter, and L. A. Jaffe. 2014. Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes. Development. 141(18): 3594-3604.
Emori, M. M. and R. Drapkin. 2014. The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis. Reprod Biol Endocrinol. 12: 60.
Fiumara, F., P. Rajasethupathy, I. Antonov, S. Kosmidis, W. S. Sossin, E. R. Kandel. 2015. MicroRNA-22 gates long-term heterosynaptic plasticity in aplysia through presynaptic regulation of CPEB and downstream targets. Cell Rep. 11(12): 1866-1875.
Franchi, A., A. Moreno-Irusta, E. M. Domínguez, A. J. Adre, and L. C. Giojalas. 2020. Extracellular vesicles from oviductal isthmus and ampulla stimulate the induced acrosome reaction and signaling events associated with capacitation in bovine spermatozoa. J Cell Biochem. 121(4): 2877-2888.
Freudzon, L., R. P. Norris, A. R. Hand, S. Tanaka, Y. Saeki, T. L. Jones, M. M. Rasenick, C. H. Berlot, L. M. Mehlmann, and L. A. Jaffe. 2005. Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the Gs G protein. J Cell Biol. 171(2): 255-265.
Futter, C. E. and I. J. White. 2007. Annexins and endocytosis. Traffic. 8: 951-958.
Gerhart, J., M. Wu, and M. Kirschner. 1984. Cell cycle dynamics of an M‐phase‐specific cytoplasmic factor in Xenopus laevis oocytes and eggs. J Cell Biol. 98: 1247–1255.
Gilchrist, G. C., A. Tscherner, T. Nalpathamkalam, D. Merico, and J. LaMarre. 2016. MicroRNA expression during bovine oocyte maturation and fertilization. Int J Mol Sci. 17(3): 396.
Gonzales, P. A., T. Pisitkun, J. D. Hoffert, D. Tchapyjnikov, R. A. Star, R. Kleta, N. S. Wang, and M. A. Knepper. 2008. Large-scale proteomics and phosphoproteomics of urinary exosomes. J Am Soc Nephrol. 20(2): 363-379.
Gould, S. J. and G. Raposo. 2013. As we wait: coping with an imperfect nomenclature for extracellular vesicles. Journal of Extracellular Vesicles. 2.
Griffiths-Jones, S., R. J. Grocock, S. van Dongen, A. Bateman, and A. J. Enright. 2006. miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids. 34: D140-D144.
Guven-Ozkan, T., S. M. Robertson, Y. Nishi, and R. Lin. 2010. zif-1 translational repression defines a second, mutually exclusive OMA function in germline transcriptional repression. Development. 137(20): 3373-3382.
Guven-Ozkan, T., Y. Nishi, S. M. Robertson, and R. Lin. 2008. Global transcriptional repression in C. elegans germline precursors by regulated sequestration of TAF-4. Cell. 135(1): 149-160.
György, B., T. G. Szabó, M. Pásztói, Z. Pál, P. Misják, B. Aradi, V. László, E. Pállinger, E. Pap, A. Kittel, G. Nagy, A. Falus, and E. I. Buzás. 2011. Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci. 68(16):2667-2688.
Hale, B. J., Y. Li, M. K. Adur, and J. W. Ross. 2020. Inhibition of germinal vesicle breakdown using IBMX increases microRNA-21 in the porcine oocyte. Reprod Biol Endocrinol. 18(1): 39.
Han, S. J., R. Chen, M. P. Paronetto, and M. Conti. 2005. Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse. Curr Biol. 15(18): 1670-1676.
Harris, E. A., K. K. Stephens, and W. Winuthayanon. 2020. Extracellular vesicles and the oviduct function. Int J Mol Sci. 21(21):8280.
He, L., X. He, L. Lim, P., E. de Stanchina, Z. Xuan, Y. Liang, W. Xue, L. Zender, J. Magnus, D. Ridzon, A. L. Jackson, P. S. Linsley, C. Chen, S. W. Lowe, M. A. Cleary, and G. J. Hannon. 2007. A microRNA component of the p53 tumour suppressor network. Nature.447: 1130-1134.
Hinckley, M., S. Vaccari, K. Horner, R. Chen, and M. Conti. 2005 The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes. Dev Biol. 287(2): 249-261.
Hossain, M. M., D. Salilew-Wondim, K. Schellander, and D. Tesfaye. 2012. The role of microRNAs in mammalian oocytes and embryos. Anim Reprod Sci. 134(1-2):36-44.
Igarashi, H., T. Takahashi, and S. Nagase. 2015. Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies. Reprod Med Biol. 14(4): 159-169.
Igea, A. and R. Méndez. 2010. Meiosis requires a translational positive loop where CPEB1 ensues its replacement by CPEB4. EMBO J. 29(13):2182-2193.
Jaffe, L. A. and J. R. Egbert. 2017. Regulation of mammalian oocyte meiosis by intercellular communication within the ovarian follicle. Annu Rev Physiol. 79: 237-260.
Janowska-Wieczorek, A., M. Wysoczynski, J. Kijowski, L. Marquez-Curtis, B. Machalinski, J. Ratajczak and M. Z. Ratajczak. 2005. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer. 113: 752-760.
Jiao, W., S. Zhao, R. Liu, T. Guo, and Y. Qin. 2020. CPEB1 deletion is not a common explanation for premature ovarian insufficiency in a Chinese cohort. J Ovarian Res. 13(1): 49.
Kaczanowska, J., F. Iftode, G. Coffe, M. Prajer, H. Kosciuszko, and A. Adoutte.1996. The protein kinase inhibitor 6-dimethylaminopurine does not inhibit micronuclear mitosis, but impairs the rearrangement of cytoplasmic MTOCs and execution of cytokinesis in the ciliate Paramecium during transition to interphase. European Journal of Protistology. 32(1): 2-17.
Karasu, M. E., N. Bouftas, S. Keeney, and K. Wassmann. 2019. Cyclin B3 promotes anaphase I onset in oocyte meiosis. J Cell Biol. 218(4):1265-1281.
Kauppila, T. E. S., J. H. K. Kauppila, and N. G. 2017. Larsson. Mammalian mitochondria and aging: an update. Cell Metab. 25: 57–71.
Keady, B. T., P. Kuo, S. E. Martínez, L. Yuan, and L. E. Hake. 2007. MAPK interacts with XGef and is required for CPEB activation during meiosis in Xenopus oocytes. J Cell Sci. 120(Pt 6): 1093-1103.
Kim, V. N. J. Han, M. C. Siomi, S. Kim, and V. N. Kim. 2009. Biogenesis of small RNAs in animals. Nat. Rev. Mol. Biol. 10: 126-139.
Knight, P. G. and C. Glister. 2006. TGF-beta superfamily members and ovarian follicle development. Reproduction. 132(2): 191-206.
Kowalczyk-Zieba, I., D. Boruszewska, K. Suwik, J. Staszkiewicz-Chodor, J. Jaworska, and I. Woclawek-Potocka. 2020. Iloprost affects in vitro maturation and developmental competence of bovine oocytes. Theriogenology. 157: 286-296.
Kozomara, A., M. Birgaoanu, and S. Griffiths-Jones. 2019. miRBase: from microRNA sequences to function. Nucleic Acids Res. 47(D1):D155-D162.
Kujoth, G. C., A. Hiona, T. D. Pugh, S. Someya, K. Panzer, S. E. Wohlgemuth, T. Hofer, A. Y. Seo, R. Sullivan, W. A. Jobling, J. D. Morrow, H. Van Remmen, J. M. Sedivy, T. Yamasoba, M. Tanokura, R. Weindruch, C. Leeuwenburgh, and T. A. Prolla. 2005. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 309: 481-484.
Leese, H. J., J. I. Tay, J. Reischl, and S. J. Downing. 2001. Formation of Fallopian tubal fluid: role of a neglected epithelium. Reproduction. 121(3): 339–46.
Lei, L., S. Jin, G. Gonzalez, R. R. Behringer, and T. K. Woodruff. 2010. The regulatory role of Dicer in folliculogenesis in mice. Mol Cell Endocrinol. 315(1-2):63-73.
Li, J., J. X. Tang, J. M. Cheng, B. Hu, Y. Q. Wang, B. Aalia, X. Y. Li, C. Jin, X. X. Wang, S. L. Deng, Y. Zhang, S. R. Chen, W. P. Qian, Q. Y. Sun, X. X. Huang, and Y. X. Liu. 2018. Cyclin B2 can compensate for Cyclin B1 in oocyte meiosis I. J Cell Biol. 217(11): 3901-3911.
Li, J., Y. C. Ouyang, C. H. Zhang, W. P. Qian, and Q. Y. Sun. 2019. The cyclin B2/CDK1 complex inhibits separase activity in mouse oocyte meiosis I. Development. 146(23): dev182519.
Li, S. and W. Winuthayanon. 2017. Oviduct: roles in fertilization and early embryo development. J Endocrinol. (1): R1-R26.
Li, Y., L. Wang, L. Zhang, Z. He, G. Feng, H. Sun, J. Wang, Z. Li, C. Liu, J. Han, J. Mao, P. Li, X. Yuan, L. Jiang, Y. Zhang, Q. Zhou, and W. Li. 2019. Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I. J Cell Biol. 218(5):1553-1563
Liu, J., M. A. Carmell, F. V. Rivas, C. G. Marsden, J. M. Thomson, J. J. Song, S. M. Hammond, L. Joshua-Tor, and G. J. Hannon. 2004. Argonaute2 Is the Catalytic Engine of Mammalian RNAi. Science. 305: 1437-1441.
Lonergan, P. and T. Fair. 2008. In vitro-produced bovine embryos—Dealing with the warts. Theriogenology.69：17-22.
Lopera-Vásquez, R., M. Hamdi, B. Fernandez-Fuertes, V. Maillo, P. Beltrán-Breña, A. Calle, A. Redruello, S. López-Martín, A. Gutierrez-Adán, M. Yañez-Mó, MÁ. Ramirez, and D. Rizos. 2016. Extracellular vesicles from boec in in vitro embryo development and quality. PLoS One: 11(2): e0148083.
Lopera-Vasquez, R., M. Hamdi, V. Maillo, A. Gutierrez-Adan, P. Bermejo-Alvarez, MÁ. Ramírez, M. Yáñez-Mó, and D. Rizos. 2017. Effect of bovine oviductal extracellular vesicles on embryo development and quality in vitro. Reproduction and Fertility. 153：461-470.
Luo, B., L. Ma, X. Xing, Z. R. Wang, Q. Teng, and S. G. Li. 2020. MiR-22-3p regulates the proliferation and invasion of Wilms' tumor cells by targeting AKT3. Eur Rev Med Pharmacol Sci. 24(11): 5996-6004.
Ma, J., Y. Yao, P. Wang, Y. Liu, L. Zhao, Z. Li, Z. Li, and Y. Xue. 2014. MiR-152 functions as a tumor suppressor in glioblastoma stem cells by targeting Krüppel-like factor 4. Cancer Lett. 355(1): 85-95.
Maidarti, M., R. A. Anderson, and E. E. Telfer. 2020. Crosstalk between PTEN/PI3K/Akt Signalling and DNA Damage in the Oocyte: Implications for Primordial Follicle Activation, Oocyte Quality and Ageing. Cells. 9(1): 200.
Mao, L., H. Lou, Y. Lou, N. Wang, and F. Jin. 2014. Behaviour of cytoplasmic organelles and cytoskeleton during oocyte maturation. Reprod Biomed Online. 28(3): 284-299.
Marangos, P., M. Stevense, K. Niaka, M. Lagoudaki, I. Nabti, R. Jessberger, and J. Carroll. 2015. DNA damage-induced metaphase I arrest is mediated by the spindle assembly checkpoint and maternal age. Nat Commun. 6: 8706.
Mathivanan, S., H. Ji and R. J. Simpson. 2010. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 73(10):1907-1920.
Mathivanan, S., J. W. Lim, B. J. Tauro, H. Ji, R. L. Moritz, and R. J. Simpson. 2010. Proteomic analysis of A33-immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics. 9(2): 197-208.
McGee, E. A. and A. J. Hsueh. 2000. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 21(2): 200-214.
Mears, R., R. A. Craven, S. Hanrahan, N. Totty, C. Upton, S. L. Young, P. Patel, P. J. Selby, and R. E. Banks. 2004. Proteomic analysis of melanoma-derived exosomes by two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Proteomics. 4: 4019-4031.
Mehlmann, L. M. 2005. Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction. 130(6): 791-799.
Mehlmann, L. M., Y. Saeki, S. Tanaka, T. J. Brennan, A. V. Evsikov, F. L. Pendola, B. B. Knowles, J. J. Eppig, and L. A. Jaffe. 2004. The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science. 306: 1947-1950.
Murchison, E. P., P. Stein, Z. Xuan, H. Pan, M. Q. Zhang, R. M. Schultz, and G. J. Hannon. 2007. Critical roles for Dicer in the female germline. Genes Dev. 21(6): 682-693.
Nagaraja, A. K., C. Andreu-Vieyra, H. L. Franco, L. Ma, R. Chen, D. Y. Han, H. Zhu, J. E. Agno, P. H. Gunaratne, F. J. DeMayo, and M. M. Matzuk. 2008. Deletion of dicer in somatic cells of the female reproductive tract causes sterility. Mol Endocrinol. 22(10): 2336-2352.
Nogueira, D., R. Ron-El, S. Friedler, M. Schachter, A. Raziel, R. Cortvrindt, and J. Smitz. 2006. Meiotic arrest in vitro by phosphodiesterase 3-inhibitor enhances maturation capacity of human oocytes and allows subsequent embryonic development. Biol Reprod. 74(1): 177-184.
Norris, R. P., W. J. Ratzan, M. Freudzon, L. M. Mehlmann, J. Krall, M. A. Movsesian, H. Wang, H. Ke, V. O. Nikolaev, and L. A. Jaffe. 2009. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 136(11): 1869-1878.
Nothias, J. Y., S. Majumder, K. J. Kaneko, and M. L. DePamphilis. 1995. Regulation of gene expression at the beginning of mammalian development. J Biol Chem. 270(38): 22077-22080.
O'Brien, K., K. Breyne, S. Ughetto, L. C. Laurent, and X. O. Breakefield. 2020. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat Rev Mol Cell Biol. 21(10):585-606.
Oksvold, M. P., A. Kullmann, L. Forfang, B. Kierulf, M. Li, A. Brech, A. V. Vlassov, E. B. Smeland, A. Neurauter, and K. W. Pedersen. 2014. Expression of B-cell surface antigens in subpopulations of exosomes released from B-cell lymphoma cells. Clin Ther. 36(6):847-862.
Pan, B. and J. Li. 2018. MicroRNA-21 up-regulates metalloprotease by down-regulating TIMP3 during cumulus cell-oocyte complex in vitro maturation. Molecular and Cellular Endocrinology. 477: 29-38
Pan, B. and J. Li. 2019. The art of oocyte meiotic arrest regulation. Reprod Biol Endocrinol. 17(1):8.
Pirino, G., M. P. Wescott, and P. J. Donovan. 2009. Protein kinase A regulates resumption of meiosis by phosphorylation of Cdc25B in mammalian oocytes. Cell Cycle 8(4): 665-670.
Pisitkun, T., R. F. Shen, and M. A. Knepper. 2004. Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci USA. 101: 13368-13373.
Potolicchio, I., G. J. Carven, X. Xu, C. Stipp, R. J. Riese, L. J. Stern, and L. Santambrogio. 2005. Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol. 175: 2237-2243.
Pugholm, L. H., A. L. Revenfeld, E. K. Søndergaard, and M. M. Jørgensen. 2015. Antibody-Based assays for phenotyping of extracellular vesicles. Biomed Res Int. 2015:524817.
Raposo, G. and W. Stoorvogel. 2013. Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol. 200(4):373-83.
Rayner, K. J., C. C. Esau, F. N. Hussain, A. L. McDaniel, S. M. Marshall, J. M. van Gils, T. D. Ray, F. J. Sheedy, L. Goedeke, X. Liu, O. G. Khatsenko, V. Kaimal, C. J. Lees, C. Fernandez-Hernando, E. A. Fisher, R. E. Temel, and K. J. Moore.2011. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Nature. 478(7369): 404-407.
Reddy, P., L. Liu, D. Adhikari, K. Jagarlamudi, S. Rajareddy, Y. Shen, C. Du, W. Tang, T. Hämäläinen, S. L. Peng, Z. J. Lan, A. J. Cooney, I. Huhtaniemi, and K. Liu. 2008. Oocyte-specific deletion of Pten causes premature activation of the primordial follicle pool. Science. 319(5863): 611-613.
Reis, A., H. Y. Chang, M. Levasseur, and K. T. Jones. 2006. APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division. Nat Cell Biol. 8: 539-540.
Revenfeld, A. L., R. Bæk, M. H. Nielsen, A. Stensballe, K. Varming, and M. Jørgensen. 2014. Diagnostic and prognostic potential of extracellular vesicles in peripheral blood. Clin Ther. 36(6):830-846.
Reza, A. M. M. T., Y. J. Choi, S. G. Han, H. Song, C. Park, K. Hong and J. H. Kim. 2019. Roles of microRNAs in mammalian reproduction: from the commitment of germ cells to peri-implantation embryos. Biol Rev Camb Philos Soc. 94(2):415-438.
Reza, A. M. M. T., Y. J. Choi, S.G. Han, H. Song, C. Park, K. Hong and J. H. Kim. 2018. Roles of microRNAs in mammalian reproduction: from the commitment of germ cells to peri‐implantation embryos. Biol Rev Camb Philos Soc. 94(2):415-438.
Rimon-Dahari, N., L. Yerushalmi-Heinemann, L. Alyagor, and N. Dekel. 2016. Ovarian Folliculogenesis. Results Probl Cell Differ. 58: 167-190.
Robker, R. L., J. D. Hennebold, and D. L. Russell. 2018. Coordination of Ovulation and Oocyte Maturation: A Good Egg at the Right Time. Endocrinology. 159(9): 3209-3218.
Saint-Dizier, M., J. Schoen, S. Chen, C. Banliat, and P. Mermillod. 2019. Composing the early embryonic microenvironment: physiology and regulation of oviductal secretions. Int J Mol Sci. 21(1): 223.
Salilew-Wondim, D., S. Gebremedhn, M. Hoelker, E. Tholen, T. Hailay and D. Tesfaye. 2020. The role of microRNAs in mammalian fertility: from gametogenesis to embryo implantation. Int J Mol Sci. 21(2):585.
Sasaki, H., T. Hamatani, S. Kamijo, M. Iwai, M. Kobanawa, S. Ogawa, K. Miyado, and M. Tanaka. 2019. Impact of oxidative stress on age-associated decline in oocyte developmental competence. Front Endocrinol (Lausanne). 10: 811.
Schuh, M. and J. Ellenberg. 2007. Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell. 130(3): 484-498.
Shojaati, G., I. Khandaker, M. L. Funderburgh, M. M. Mann, R. Basu, D. B. Stolz, M. L. Geary, A. Dos Santos, S. X. Deng, and J. L. Funderburgh. 2019. Mesenchymal stem cells reduce corneal fibrosis and inflammation via extracellular vesicle-mediated delivery of miRNA. Stem Cells Transl Med. 8(11): 1192-1201.
Shuhaibar, L. C., J. R. Egbert, A. B. Edmund, T. F. Uliasz, D. M. Dickey, S. P. Yee, L. R. Potter, and L. A. Jaffe. 2016. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone. Dev Biol. 409(1): 194-201.
Sohel, M. M., M. Hoelker, S. S. Noferesti, D. Salilew-Wondim, E. C. Tholen, Looft, F. Rings, M. J. Uddin, T. E. Spencer, K. Schellander, and D. Tesfaye. 2013. Exosomal and non-exosomal transport of extra-cellular micrornas in follicular fluid: implications for bovine oocyte developmental competence. PLoS One. 8(11): e78505.
Sousa Martins, J. P., X. Liu, A. Oke, R. Arora, F. Franciosi, S. Viville, D. J. Laird, J. C. Fung, and M. Conti. 2016. DAZL and CPEB1 regulate mRNA translation synergistically during oocyte maturation. J Cell Sci. 129(6): 1271-1282.
Stenmark, H. 2009. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 10: 513-525.
Suarez, S. S. 2016. Mammalian sperm interactions with the female reproductive tract. Cell Tissue Res. 363(1): 185-194.
Sun, J., X. Tian, J. Zhang, Y. Huang, X. Lin, L. Chen, and S. Zhang. 2017. Regulation of human glioma cell apoptosis and invasion by miR-152-3p through targeting DNMT1 and regulating NF2: MiR-152-3p regulate glioma cell apoptosis and invasion. J Exp Clin Cancer Res. 36(1): 100.
Sun, X. F., Y. P. Li, B. Pan, Y. F. Wang, J. Li, and W. Shen. 2018. Molecular regulation of miR-378 on the development of mouse follicle and the maturation of oocyte in vivo. Cell Cycle. 17(18): 2230-2242.
Susko-Parrish, J. L., M. L. Leibfried Rutledge, D. L. Northey, V. Schutzkus, and N. L. First. 1994. Inhibition of protein kinases after an induced calcium transient causes transition of bovine oocytes to embryonic cycles without meiotic completion. Dev. Biol. 166: 729-739.
Szollosi, M. S., J. Z. Kubiak, P. Debey, H. de Pennart, D. Szollosi, and B. Maro. 1993. Inhibition of protein kinases by 6-dimethylaminopurine accelerates the transition to interphase in activated mouse oocytes. J. Cell Sci. 104: 861-872.
Taganov, K. D., M. P. Boldin, K. J. Chang, and D. Baltimore, 2006. NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A. 103(33): 12481-12486.
Tannetta, D., R. Dragovic, Z. Alyahyaei, and J. Southcombe. 2014. Extracellular vesicles and reproduction promotion of successful pregnancy. Cell Mol Immunol. 11: 548-563.
Thery, C., M. Boussac, P. Veron, P. Ricciardi-Castagnoli, G. Raposo, J. Garin and S. Amigorena. 2001. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol. 166: 7309-7318.
Thery, C., M. Boussac, P. Veron, P. Ricciardi-Castagnoli, G. Raposo, J. Garin, and S. Amigorena. 2001. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol. 166: 7309-7318.
Théry, C., M. Ostrowski and E. Segura. 2009. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 9(8):581-593.
Tie, Y., C. Chen, Y. Yang, Z. Qian, H. Yuan, H. Wang, H. Tang, Y. Peng, X. Du, and B. Liu. 2018. Upregulation of let-7f-5p promotes chemotherapeutic resistance in colorectal cancer by directly repressing several pro-apoptotic proteins. Oncol Lett. 15(6): 8695-8702.
Tsafriri, A., S. Y. Chun, R. Zhang, A. J. Hsueh, and M. Conti. 1996. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol. 178(2): 393-402.
Vaccari, S., J. L. 2nd Weeks, M. Hsieh, F. S. Menniti, and M. Conti. 2009. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 81(3): 595-604.
Van Blerkom, J. 2011. Mitochondrial function in the human oocyte and embryo and their role in developmental competence. Mitochondrion. 11: 797–813.
Vander Borght, M and C. Wyns. 2018. Fertility and infertility: Definition and epidemiology. Clinical Biochemistry. 62：2-10.
Voronina, E. and G. M. Wesse. 2003. The regulation of oocyte maturation. Curr Top Dev Biol. 58: 53-110.
Wahid, F., A. Shehzad, T. Khan, and Y. Y. Kim. 2010. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 1803: 1231-1243.
Wang, X., Y. Wang, M. Kong, and J. Yang. 2020. MiR-22-3p suppresses sepsis-induced acute kidney injury by targeting PTEN. Biosci Rep. 40(6): BSR20200527.
Wang, Y., J. Li, F. Dong, W. Yue, Y. C. Ouyang, Z. B. Wang, Y. Hou, H. Schatten, and Q. Y. Sun. 2020. CENP-T regulates both the G2/M transition and anaphase entry by acting through CDH1 in meiotic oocytes. J Cell Sci. 133(3): jcs238105.
Waqas, M. Y., Q. Zhang, N. Ahmed, P. Yang, G. Xing, M. Akhtar, A. Basit, T. Liu, C. Hong, M. Arshad, H. M. S. Rahman, and Q. Chen. 2017. Cellular Evidence of exosomes in the reproductive tract of chinese soft-shelled turtle pelodiscus sinensis. J Exp Zool A Ecol Integr Physiol. 327(1): 18-27.
Welch, C., Y. Chen, and R. L. Stallings. 2007. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 26(34): 5017-22.
Wells, D. N., P. M. Misica, and H. R. Tervit. 1999. Production of cloned calves following nuclear transfer with cultured adult mural granulosa cells. Biol. Reprod. 60: 996-1005.
Wen, D., L. A. Banaszynski, Y. Liu, F. Geng, K. M. Noh, J. Xiang, O. Elemento, Z. Rosenwaks, C. D. Allis, and S. Rafii. 2014. Histone variant H3.3 is an essential maternal factor for oocyte reprogramming. Proc Natl Acad Sci U S A. 111(20): 7325-7330.
Wilczynska, A., A. Git, J. Argasinska, E. Belloc, and N. Standart. 2016. CPEB and miR-15/16 co-regulate translation of Cyclin E1 mRNA during xenopus oocyte maturation. PLoS One. 11(2): e0146792.
Xu, Y. W., B. Wang, C. H. Ding, T. Li, F. Gu, and C. Zhou. 2011. Differentially expressed micoRNAs in human oocytes. J Assist Reprod Genet. 28(6): 559-566.
Yanagida, K., Y. Fujikura, and H. Katayose. 2008. The present status of artificial oocyte activation in assisted reproductive technology. Reprod Med Biol. 7(3): 133-142.
Yáñez-Mó, M., P. R. Siljander, Z. Andreu, A. B. Zavec, F.E. Borràs, E. I. Buzas, K. Buzas, E. Casal, F. Cappello, J. Carvalho, E. Colás, A. Cordeiro-da Silva, S. Fais, J. M. Falcon-Perez, I. M. Ghobrial, B. Giebel, M. Gimona, M. Graner, I. Gursel, M. Gursel, N. H. Heegaard, A. Hendrix, P. Kierulf, K. Kokubun, M. Kosanovic, V. Kralj-Iglic, E. M. Krämer-Albers, S. Laitinen, C. Lässer, T. Lener, E. Ligeti, A. Linē, G. Lipps, A. Llorente, J. Lötvall, M. Manček-Keber, A. Marcilla, M. Mittelbrunn, I. Nazarenko, E. N. Nolte-'t Hoen, T. A. Nyman, L. O'Driscoll, M. Olivan, C. Oliveira, É. Pállinger, H. A. Del Portillo, J. Reventós, M. Rigau, E. Rohde, M. Sammar, F. Sánchez-Madrid, N. Santarém, K. Schallmoser, M. S. Ostenfeld, W. Stoorvogel, R. Stukelj, S. G. Van der Grein, M. H. Vasconcelos, M. H. Wauben and O. De Wever. 2015. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 4: 27066.
Yuta, M., O. Asuka, A F. Yoshie., Y. Kazuma, F. Wataru, N. Kunihiko, and S. Koji. 2017. Effects of exosome-like vesicles on cumulus expansion in pigs in vitro. J Reprod Dev. 63(1): 51-58.
Zakhartchenko, V., G. Durcova-Hills, M. Stojkovic, W. Schernthaner, K. Prelle, R. Steinborn, M. Muller, G. Brem, and E. Wolf. 1999. Effects of serum starvation and recloning on the efficiency of nuclear transfer using bovine fetal fibroblasts. J. Reprod. Fertil. 115: 325-331.
Zeng, J., L. Zhu, J. Liu, T. Zhu, Z. Xie, X. Sun, and H. Zhang. 2019. Metformin protects against oxidative stress injury induced by ischemia/reperfusion via regulation of the lncRNA-H19/miR-148a-3p/Rock2 Axis. Oxid Med Cell Longev. 2019: 8768327.
Zhang, J., Y. L. Zhang, L. W. Zhao, S. B. Pi, S. Y. Zhang, C. Tong, and H. Y. Fan. 2020. The CRL4-DCAF13 ubiquitin E3 ligase supports oocyte meiotic resumption by targeting PTEN degradation. Cell Mol Life Sci. 77(11): 2181-2197.
Zhang, P., K. Bill, J. Liu, E. Young, T. Peng, S. Bolshakov, A. Hoffman, Y. Song, E. G. Demicco, D. L. Terrada, C. J. Creighton, M. L. Anderson, A. J. Lazar, G. G. Calin, R. E. Pollock, and D. Lev. 2012. MiR-155 is a liposarcoma oncogene that targets casein kinase-1alpha and enhances beta-catenin signaling. Cancer Res. 72(7): 1751-1762.