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Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE (Open Access)

Extracellular vesicles derived from donor oviduct fluid improved birth rates after embryo transfer in mice

Pengxiang Qu A B * , Yuelei Zhao A * , Rong Wang A , Yali Zhang A , Lu Li A , Jianglin Fan C and Enqi Liu A B D
+ Author Affiliations
- Author Affiliations

A Laboratory Animal Centre, Xi’an Jiaotong University Health Science Centre, Xi’an, Shaanxi 710061, China.

B Research Institute of Atherosclerotic Disease, Xi’an Jiaotong University Cardiovascular Research Centre, Xi’an, Shaanxi 710061, China.

C Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.

D Corresponding author. Email: liuenqi@mail.xjtu.edu.cn

Reproduction, Fertility and Development 31(2) 324-332 https://doi.org/10.1071/RD18203
Submitted: 8 January 2018  Accepted: 7 July 2018   Published: 10 September 2018

Journal compilation © CSIRO 2019 Open Access CC BY-NC-ND

Abstract

Embryo transfer (ET) is an important procedure for assisted reproduction. However, the relatively lower success rate of ET hampers its application potential. In this study we aimed to elucidate the effects of extracellular vesicles derived from donor oviduct fluid (EDOF) on embryo development after ET. Extracellular vesicles from the oviduct were isolated and purified using ultracentrifugation and identified using transmission electron microscopy, NanoSight, bicinchoninic acid (BCA) protein assay and western blotting. The results revealed that extracellular vesicles were present in donor oviduct fluid in higher concentrations (P < 0.05) and contained more proteins (P < 0.05) than extracellular vesicles derived from recipient oviduct fluid (EROF). EDOF or EROF were supplemented in an ET medium (ETM) and the results showed that EDOF significantly improved birth rate via resisting apoptosis and promoting differentiation. In conclusion, our study indicated that there are differences in EDOF and EROF and that supplementing EDOF to ETM can improve the efficiency of ET; improved ET efficiency promotes the use of gene editing and benefits assisted reproductive technology and animal welfare.

Additional keywords: ammonium, apoptosis, differentiation, embryo transfer.


References

Al-Dossary, A. A., Strehler, E. E., and Martin-Deleon, P. A. (2013). Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm. PLoS One 8, e80181.
Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm.Crossref | GoogleScholarGoogle Scholar |

Alminana, C., Corbin, E., Tsikis, G., Alcantara-Neto, A. S., Labas, V., Reynaud, K., Galio, L., Uzbekov, R., Garanina, A. S., Druart, X., and Mermillod, P. (2017). Oviduct extracellular vesicles protein content and their role during oviduct–embryo cross-talk. Reproduction 154, 153–168.
Oviduct extracellular vesicles protein content and their role during oviduct–embryo cross-talk.Crossref | GoogleScholarGoogle Scholar |

Bin Ali, R., van der Ahe, F., Braumuller, T. M., Pritchard, C., Krimpenfort, P., Berns, A., and Huijbers, I. J. (2014). Improved pregnancy and birth rates with routine application of nonsurgical embryo transfer. Transgenic Res. 23, 691–695.
Improved pregnancy and birth rates with routine application of nonsurgical embryo transfer.Crossref | GoogleScholarGoogle Scholar |

Bromfield, J. J., Schjenken, J. E., Chin, P. Y., Care, A. S., Jasper, M. J., and Robertson, S. A. (2014). Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring. Proc. Natl. Acad. Sci. USA 111, 2200–2205.
Maternal tract factors contribute to paternal seminal fluid impact on metabolic phenotype in offspring.Crossref | GoogleScholarGoogle Scholar |

da Silveira, J. C., Carnevale, E. M., Winger, Q. A., and Bouma, G. J. (2014). Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare. Reprod. Biol. Endocrinol. 12, 44.
Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare.Crossref | GoogleScholarGoogle Scholar |

da Silveira, J. C., Winger, Q. A., Bouma, G. J., and Carnevale, E. M. (2015). Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-beta signalling during follicle development in the mare. Reprod. Fertil. Dev. 27, 897–905.
Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-beta signalling during follicle development in the mare.Crossref | GoogleScholarGoogle Scholar |

Exley, G. E., Tang, C., McElhinny, A. S., and Warner, C. M. (1999). Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos. Biol. Reprod. 61, 231–239.
Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos.Crossref | GoogleScholarGoogle Scholar |

Familari, M., Cronqvist, T., Masoumi, Z., and Hansson, S. R. (2017). Placenta-derived extracellular vesicles: their cargo and possible functions. Reprod. Fertil. Dev. 29, 433–447.
Placenta-derived extracellular vesicles: their cargo and possible functions.Crossref | GoogleScholarGoogle Scholar |

Gardner, D. K., and Lane, M. (1993). Amino acids and ammonium regulate mouse embryo development in culture. Biol. Reprod. 48, 377–385.
Amino acids and ammonium regulate mouse embryo development in culture.Crossref | GoogleScholarGoogle Scholar |

Gonzalez-Jara, P., Fontela, T., Lopez-Mimbela, E., Cereceda, M., Del Olmo, D., and Moreno, M. (2017). Optimization of the balance between effort and yield in unilateral surgical transfer of mouse embryos. Lab. Anim. 51, 622–628.
Optimization of the balance between effort and yield in unilateral surgical transfer of mouse embryos.Crossref | GoogleScholarGoogle Scholar |

Guillemin, Y., Lalle, P., Gillet, G., Guerin, J. F., Hamamah, S., and Aouacheria, A. (2009). Oocytes and early embryos selectively express the survival factor BCL2L10. J. Mol. Med. 87, 923–940.
Oocytes and early embryos selectively express the survival factor BCL2L10.Crossref | GoogleScholarGoogle Scholar |

Hasegawa, A., Mochida, K., Ogonuki, N., Hirose, M., Tomishima, T., Inoue, K., and Ogura, A. (2017). Efficient and scheduled production of pseudopregnant female mice for embryo transfer by estrous cycle synchronization. J. Reprod. Dev. 63, 539–545.
Efficient and scheduled production of pseudopregnant female mice for embryo transfer by estrous cycle synchronization.Crossref | GoogleScholarGoogle Scholar |

Josa, S., Seruggia, D., Fernandez, A., and Montoliu, L. (2016). Concepts and tools for gene editing. Reprod. Fertil. Dev. 29, 1–7.
Concepts and tools for gene editing.Crossref | GoogleScholarGoogle Scholar |

Koutroli, E., Alexakos, P., Kakazanis, Z., Symeon, I., Balafas, E., Voyiatzaki, C., and Kostomitsopoulos, N. (2014). Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery. Lab Anim. (NY) 43, 167–172.
Effects of using the analgesic tramadol in mice undergoing embryo transfer surgery.Crossref | GoogleScholarGoogle Scholar |

Lane, M., and Gardner, D. K. (2003). Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse. Biol. Reprod. 69, 1109–1117.
Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse.Crossref | GoogleScholarGoogle Scholar |

Lane, M., Hooper, K., and Gardner, D. K. (2001). Effect of essential amino acids on mouse embryo viability and ammonium production. J. Assist. Reprod. Genet. 18, 519–525.
Effect of essential amino acids on mouse embryo viability and ammonium production.Crossref | GoogleScholarGoogle Scholar |

Le Bin, G. C., Munoz-Descalzo, S., Kurowski, A., Leitch, H., Lou, X., Mansfield, W., Etienne-Dumeau, C., Grabole, N., Mulas, C., Niwa, H., Hadjantonakis, A. K., and Nichols, J. (2014). Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst. Development 141, 1001–1010.
Oct4 is required for lineage priming in the developing inner cell mass of the mouse blastocyst.Crossref | GoogleScholarGoogle Scholar |

Lee, K. F., Yao, Y. Q., Kwok, K. L., Xu, J. S., and Yeung, W. S. (2002). Early developing embryos affect the gene expression patterns in the mouse oviduct. Biochem. Biophys. Res. Commun. 292, 564–570.
Early developing embryos affect the gene expression patterns in the mouse oviduct.Crossref | GoogleScholarGoogle Scholar |

Li, H. W., Liao, S. B., Chiu, P. C., Tam, W. W., Ho, J. C., Ng, E. H., Ho, P. C., Yeung, W. S., Tang, F., and O., W. S. (2010). Expression of adrenomedullin in human oviduct, its regulation by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium. J. Clin. Endocrinol. Metab. 95, E18–E25.
Expression of adrenomedullin in human oviduct, its regulation by the hormonal cycle and contact with spermatozoa, and its effect on ciliary beat frequency of the oviductal epithelium.Crossref | GoogleScholarGoogle Scholar |

Lin, T., Diao, Y. F., Kang, J. W., Lee, J. E., Kim, D. K., and Jin, D. I. (2015). Tauroursodeoxycholic acid improves the implantation and live-birth rates of mouse embryos. Reprod. Biol. 15, 101–105.
Tauroursodeoxycholic acid improves the implantation and live-birth rates of mouse embryos.Crossref | GoogleScholarGoogle Scholar |

Lopez, M. J., Garcia, D., Rodriguez, A., Colodron, M., Vassena, R., and Vernaeve, V. (2014). Individualized embryo transfer training: timing and performance. Hum. Reprod. 29, 1432–1437.
Individualized embryo transfer training: timing and performance.Crossref | GoogleScholarGoogle Scholar |

Lopez-Cardona, A. P., Fernandez-Gonzalez, R., Perez-Crespo, M., Alen, F., de Fonseca, F. R., Orio, L., and Gutierrez-Adan, A. (2015). Effects of synchronous and asynchronous embryo transfer on postnatal development, adult health, and behavior in mice. Biol. Reprod. 93, 85.
Effects of synchronous and asynchronous embryo transfer on postnatal development, adult health, and behavior in mice.Crossref | GoogleScholarGoogle Scholar |

Machtinger, R., Laurent, L. C., and Baccarelli, A. A. (2016). Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum. Reprod. Update 22, 182–193.

Maillo, V., Sanchez-Calabuig, M. J., Lopera-Vasquez, R., Hamdi, M., Gutierrez-Adan, A., Lonergan, P., and Rizos, D. (2016). Oviductal response to gametes and early embryos in mammals. Reproduction 152, R127–R141.
Oviductal response to gametes and early embryos in mammals.Crossref | GoogleScholarGoogle Scholar |

Miller, D. J. (2015). Regulation of sperm function by oviduct fluid and the epithelium: insight into the role of glycans. Reprod Domest Anim. 50, 31–39.
Regulation of sperm function by oviduct fluid and the epithelium: insight into the role of glycans.Crossref | GoogleScholarGoogle Scholar |

Ng, Y. H., Rome, S., Jalabert, A., Forterre, A., Singh, H., Hincks, C. L., and Salamonsen, L. A. (2013). Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo–endometrial cross talk at implantation. PLoS One 8, e58502.
Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo–endometrial cross talk at implantation.Crossref | GoogleScholarGoogle Scholar |

Proudfoot, C., Carlson, D. F., Huddart, R., Long, C. R., Pryor, J. H., King, T. J., Lillico, S. G., Mileham, A. J., McLaren, D. G., Whitelaw, C. B., and Fahrenkrug, S. C. (2015). Genome edited sheep and cattle. Transgenic Res. 24, 147–153.
Genome edited sheep and cattle.Crossref | GoogleScholarGoogle Scholar |

Qu, P., Qing, S., Liu, R., Qin, H., Wang, W., Qiao, F., Ge, H., Liu, J., Zhang, Y., Cui, W., and Wang, Y. (2017). Effects of embryo-derived exosomes on the development of bovine cloned embryos. PLoS One 12, e0174535.
Effects of embryo-derived exosomes on the development of bovine cloned embryos.Crossref | GoogleScholarGoogle Scholar |

Santonocito, M., Vento, M., Guglielmino, M. R., Battaglia, R., Wahlgren, J., Ragusa, M., Barbagallo, D., Borzi, P., Rizzari, S., Maugeri, M., Scollo, P., Tatone, C., Valadi, H., Purrello, M., and Di Pietro, C. (2014). Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation. Fertil Steril. 102, 1751–1761.e1.
Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation.Crossref | GoogleScholarGoogle Scholar |

Schjenken, J. E., and Robertson, S. A. (2015). Seminal fluid signalling in the female reproductive tract: implications for reproductive success and offspring health. Adv. Exp. Med. Biol. 868, 127–158.
Seminal fluid signalling in the female reproductive tract: implications for reproductive success and offspring health.Crossref | GoogleScholarGoogle Scholar |

Simons, M., and Raposo, G. (2009). Exosomes – vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 21, 575–581.
Exosomes – vesicular carriers for intercellular communication.Crossref | GoogleScholarGoogle Scholar |

Tan, W., Proudfoot, C., Lillico, S. G., and Whitelaw, C. B. (2016). Gene targeting, genome editing: from Dolly to editors. Transgenic Res. 25, 273–287.
Gene targeting, genome editing: from Dolly to editors.Crossref | GoogleScholarGoogle Scholar |

Thery, C., Amigorena, S., Raposo, G., and Clayton, A. (2006). Isolation and characterization of exosomes from cell culture supernatants and biological fluids. In ‘Current protocols in cell biology’. pp. 3.22.1–3.22.29. (Wiley: New York.)

Weber, J. A., Freeman, D. A., Vanderwall, D. K., and Woods, G. L. (1991). Prostaglandin E2 secretion by oviductal transport-stage equine embryos. Biol. Reprod. 45, 540–543.
Prostaglandin E2 secretion by oviductal transport-stage equine embryos.Crossref | GoogleScholarGoogle Scholar |