Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 33, Issue 3, pp 303–311 | Cite as

Exosome-mediated communication in the ovarian follicle

  • C. Di Pietro
Review

Abstract

Cells are able to produce and release different types of vesicles, such as microvesicles and exosomes, in the extracellular microenvironment. According to the scientific community, both microvesicles and exosomes are able to take on and transfer different macromolecules from and to other cells, and in this way, they can influence the recipient cell function. Among the different macromolecule cargos, the most studied are microRNAs. MicroRNAs are a large family of non-coding RNAs involved in the regulation of gene expression. They control every cellular process and their altered regulation is involved in human diseases. Their presence in mammalian follicular fluid has been recently demonstrated, and here, they are enclosed within microvesicles and exosomes or they can also be associated to protein complexes. The presence of microvesicles and exosomes carrying microRNAs in follicular fluid could represent an alternative mechanism of autocrine and paracrine communication inside the ovarian follicle. The outcomes from these studies could be important in basic reproductive research but could also be useful for clinical application. In fact, the characterization of extracellular vesicles in follicular fluid could improve reproductive disease diagnosis and provide biomarkers of oocyte quality in ART (Assisted Reproductive Treatment).

Keywords

Extracellular vesicles Exosomes MicroRNAs Ovarian follicle 

Notes

Acknowledgments

The author wishes to thank M Vento and M Purrello with whom she shares her research work. She wishes to thank R Battaglia and the lab staff for their contribution and the Scientific Bureau of the University of Catania for language support.

Compliance with ethical standards

Conflict of interest

The author declares that she has no competing interests.

References

  1. 1.
    Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015. doi: 10.3402/jev.v4.27066.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Lee Y, El Andaloussi S, Wood MJ. Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy. Hum Mol Genet. 2012;21(R1):R125–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654–9.CrossRefPubMedGoogle Scholar
  4. 4.
    Lo Cicero A, Stahl PD, Raposo G. Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr Opin Cell Biol. 2015. doi: 10.1016/j.ceb.2015.04.013.PubMedGoogle Scholar
  5. 5.
    Corrado C, Raimondo S, Chiesi A, Ciccia F, De Leo G, Alessandro R. Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sc. 2013. doi: 10.3390/ijms14035338.Google Scholar
  6. 6.
    Ragusa M, Barbagallo D, Purrello M. Exosomes: nanoshuttles to the future of BioMedicine. Cell Cycle. 2015. doi: 10.1080/15384101.2015.1006535.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Antonyak MA, Cerione RA. Emerging picture of the distinct traits and functions of microvesicles and exosomes. Proc Natl Acad Sci U S A. 2015;112(12):3589–90. doi: 10.1073/pnas.1502590112. Epub 2015 Mar 11.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Kanada M, Bachmann MH, Hardy JW, Frimannson DO, Bronsart L, Wang A, et al. Contag CH Differential fates of biomolecules delivered to target cells via extracellular vesicles. Proc Natl AcadSci U S A. 2015;112(12):E1433–42. doi: 10.1073/pnas.1418401112. Epub 2015 Feb 23.Google Scholar
  9. 9.
    Fu XD. Non-coding RNA: a new frontier in regulatory biology. Natl Sci Rev. 2014;1:190–204.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  11. 11.
    Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10:704–14. doi: 10.1038/nrg2634.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56:1733–41. doi: 10.1373/clinchem.2010.147405.CrossRefPubMedGoogle Scholar
  13. 13.
    Cortez MA, Bueso-Ramos C, Ferdin J. Lopez-Berestein G. CalinGA. MicroRNAs in body fluids--the mix of hormones and biomarkers. Nat Rev ClinOncol: Sood AK; 2011. doi: 10.1038/nrclinonc.2011.76.Google Scholar
  14. 14.
    Kosaka N, Yoshioka Y, Hagiwara K, Tominaga N, Katsuda T, Ochiya T. Trash or treasure: extracellular microRNAs and cell-to-cell communication. Front Genet. 2013. doi: 10.3389/fgene.2013.00173.PubMedPubMedCentralGoogle Scholar
  15. 15.
    McGinnis LK, Luense LJ, Christenson LK. MicroRNA in ovarian biology and disease. Cold Spring HarbPerspect Med. 2015. doi: 10.1101/cshperspect.a022962.Google Scholar
  16. 16.
    Li Y, Fang Y, Liu Y, Yang X. MicroRNAs in ovarian function and disorders. J Ovarian Res. 2015;8:51. doi: 10.1186/s13048-015-0162-2.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Hutt KJ, Albertini DF. An oocentric view of folliculogenesis and embryogenesis. Reprod Biomed Online. 2007;14:758–64.CrossRefPubMedGoogle Scholar
  18. 18.
    Zuccotti M, Merico V, Cecconi S, Redi CA, Garagna S. What does it take to make a developmentally competent mammalian egg? Hum Reprod Update. 2011. doi: 10.1093/humupd/dmr009.PubMedGoogle Scholar
  19. 19.
    Sun QY, Miao YL, Schatten H. Towards a new understanding on the regulation of mammalian oocyte meiosis resumption. Cell Cycle. 2009;8:2741–7.CrossRefPubMedGoogle Scholar
  20. 20.
    Reddy P, Zheng W, Liu K. Mechanisms maintaining the dormancy and survival of mammalian primordial follicles. Trends Endocrinol Metab. 2010. doi: 10.1016/j.tem.2009.10.001.PubMedGoogle Scholar
  21. 21.
    Fragouli E, Lalioti MD, Wells D. The transcriptome of follicular cells: biological insights and clinical implications for the treatment of infertility. Hum Reprod Update. 2014. doi: 10.1093/humupd/dmt044.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Zamah AM, Hsieh M, Chen J, Vigne JL, Rosen MP, Cedars MI, et al. Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin. Hum Reprod. 2010. doi: 10.1093/humrep/deq212.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Russell DL, Robker RL. Molecular mechanisms of ovulation: co-ordination through the cumulus complex. Hum Reprod Update. 2007;13:289–312.CrossRefPubMedGoogle Scholar
  24. 24.
    Revelli A, Delle Piane L, Casano S, Molinari E, Massobrio M, Rinaudo P. Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol. 2009. doi: 10.1186/1477-7827-7-40.Google Scholar
  25. 25.
    Rodgers RJ, Irving-Rodgers HF. Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod. 2010;82:1021–9.CrossRefPubMedGoogle Scholar
  26. 26.
    da Silveira JC, Veeramachaneni DN, Winger QA, Carnevale EM, Bouma GJ. 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. 2012. doi: 10.1095/biolreprod.111.093252.PubMedGoogle Scholar
  27. 27.
    Sohel MM, Hoelker M, Noferesti SS, Salilew-Wondim D, Tholen E, Looft C, et al. Exosomal and non-exosomal transport of extra-cellular microRNAs in follicular fluid: implications for bovine oocyte developmental competence. PLoS One. 2013. doi: 10.1371/journal.pone.0078505.Google Scholar
  28. 28.
    da Silveira JC, Carnevale EM, Winger QA, Bouma GJ. Regulation of ACVR1 and ID2 by cell-secreted exosomes during follicle maturation in the mare. Reprod Biol Endocrinol. 2014. doi: 10.1186/1477-7827-12-44.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Diez-Fraile A, Lammens T, Tilleman K, Witkowski W, Verhasselt B, De Sutter P, et al. Age-associated differential microRNA levels in human follicular fluid reveal pathways potentially determining fertility and success of in vitro fertilization. Hum Fertil (Camb). 2014. doi: 10.3109/14647273.2014.897006.Google Scholar
  30. 30.
    Santonocito M, Vento M, Guglielmino MR, Battaglia R, Wahlgren J, Ragusa M, et al. 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. 2014. doi: 10.1016/j.fertnstert.2014.08.005.PubMedGoogle Scholar
  31. 31.
    da Silveira JC, de Andrade GM, Nogueira MF, Meirelles FV, Perecin F. Involvement of miRNAs and cell-secreted vesicles in mammalian ovarian antral follicle development. Reprod Sci. 2015. doi: 10.1177/1933719115574344.PubMedGoogle Scholar
  32. 32.
    da Silveira JC, Winger QA, Bouma GJ, Carnevale EM. Effects of age on follicular fluid exosomal microRNAs and granulosa cell transforming growth factor-? signalling during follicle development in the mare. Reprod Fertil Dev. 2015. doi: 10.1071/RD14452.Google Scholar
  33. 33.
    Hung WT, Hong X, Christenson LK, McGinnis LK. Extracellular vesicles from bovine follicular fluid support cumulus expansion. Biol Reprod. 2015 . pii: biolreprod.115.132977.Google Scholar
  34. 34.
    Urbanelli L, Magini A, Buratta S, Brozzi A, Sagini K, Polchi A, et al. Signaling pathways in exosomes biogenesis. Secretion and Fate Genes. 2013. doi: 10.3390/genes4020152.PubMedGoogle Scholar
  35. 35.
    Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262:9412–20.PubMedGoogle Scholar
  36. 36.
    Raposo G. NijmanHW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, GeuzeHJ.B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183:1161–72.CrossRefPubMedGoogle Scholar
  37. 37.
    Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2088;319:1244–7.CrossRefGoogle Scholar
  38. 38.
    Van Niel G, Charrin S, Simoes S, Romao M, Rochin L, Saftig P, et al. The tetraspaninCD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev Cell. 2011;21:708–21.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Zhang J, Li S, Li L, Li M, Guo C, Yao J, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinforma. 2015;13(1):17–24. doi: 10.1016/j.gpb.2015.02.001. Epub 2015 Feb 24. Review.CrossRefGoogle Scholar
  40. 40.
    Emmanouilidou E, Melachroinou K, Roumeliotis T, Garbis SD, Ntzouni M, Margaritis LH, et al. Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J Neurosc. 2010. doi: 10.1523/JNEUROSCI.5699-09.2010.Google Scholar
  41. 41.
    Yu X, Harris SL, Levine AJ. The regulation of exosome secretion: a novel function of the p53 protein. Cancer Res. 2006;66(9):4795–801.CrossRefPubMedGoogle Scholar
  42. 42.
    Sang Q, Yao Z, Wang H, Feng R, Wang H, Zhao X, et al. Identification of microRNAs in human follicular fluid: characterization of microRNAs that govern steroidogenesis in vitro and are associated with polycystic ovary syndrome in vivo. J Clin Endocrinol Metab. 2013. doi: 10.1210/jc.2013-1715.Google Scholar
  43. 43.
    Schauer SN, Sontakke SD, Watson ED, Esteves CL, Donadeu FX. Involvement of miRNAs in equine follicle development. Reproduction. 2013. doi: 10.1530/REP-13-0107.PubMedGoogle Scholar
  44. 44.
    Donadeu FX. SchauerSN. Domest Anim Endocrinol: Differential miRNA expression between equine ovulatory and anovulatory follicles; 2013. doi: 10.1016/j.domaniend.2013.06.006.Google Scholar
  45. 45.
    Roth LW, Mc Callie B, Alvero R, Schoolcraft WB, Minjarez D, Katz-Jaffe MG. Altered microRNA and gene expression in the follicular fluid of women with polycystic ovary syndrome. J Assist Reprod Genet. 2014. doi: 10.1007/s10815-013-0161-4.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Yin M, Wang X, Yao G, Lü M, Liang M, Sun Y, et al. Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins. J Biol Chem. 2014. doi: 10.1074/jbc.M113.546044.Google Scholar
  47. 47.
    Feng R, Sang Q, Zhu Y, Fu W, Liu M, Xu Y, et al. MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro. Sci Rep. 2015. doi: 10.1038/srep08689.Google Scholar
  48. 48.
    Moreno JM, Núñez MJ, Quiñonero A, Martínez S, de la Orden M, Simón C, et al. Follicular fluid and mural granulosa cells microRNA profiles vary in in vitro fertilization patients depending on their age and oocyte maturation stage. Fertil Steril. 2015. doi: 10.1016/j.fertnstert.2015.07.001.PubMedGoogle Scholar
  49. 49.
    Sørensen AE, Wissing ML, Salö S, Englund AL, Dalgaard LT. MicroRNAs related to polycystic ovary syndrome (PCOS). Genes (Basel). 2014. doi: 10.3390/genes5030684.PubMedCentralGoogle Scholar
  50. 50.
    Li Q, Shao Y, Zhang X, Zheng T, Miao M, Qin L, et al. Plasma long noncoding RNA protected by exosomes as a potential stable biomarker for gastric cancer. Tumour Biol. 2015. doi: 10.1007/s13277-014-2807-y.Google Scholar
  51. 51.
    Falcieri E, Battistin L, Agnati LF, Stocchi V. C2C12 myoblasts release micro-vesicles containing mtDNA and proteins involved in signal transduction. Exp Cell Res. 2010;316:1977–84.CrossRefPubMedGoogle Scholar
  52. 52.
    Watanabe T, Totoki Y, Toyoda A, Kaneda M, Kuramochi-Miyagawa S, Obata Y, et al. Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes. Nature. 2008. doi: 10.1038/nature06908.Google Scholar
  53. 53.
    Kandere-Grzybowska K, Letourneau R, Kempuraj D, Donelan J, Poplawski S, Boucher W, et al. IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells. J Immunol. 2003;171:4830–6.CrossRefPubMedGoogle Scholar
  54. 54.
    Zolti M, Ben-Rafael Z, Meirom R, Shemesh M, Bider D, Mashiach S, et al. Cytokine involvement in oocytes and early embryos. Fertil Steril. 1991;56:265–72.PubMedGoogle Scholar
  55. 55.
    Field SL, Dasgupta T, Cummings M, Orsi NM. Cytokines in ovarian folliculogenesis, oocyte maturation and luteinisation. Mol Reprod Dev. 2014.Google Scholar
  56. 56.
    Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 2012;14:1036–45.CrossRefPubMedGoogle Scholar
  57. 57.
    Richards JS, Russell DL, Ochsner S, Hsieh M, Doyle KH, Falender AE, et al. Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization. Recent Prog Horm Res. 2002;57:195–220.CrossRefPubMedGoogle Scholar
  58. 58.
    Lichner Z, Páll E, Kerekes A, Pállinger E, Maraghechi P, Bosze Z, et al. The miR-290-295 cluster promotes pluripotency maintenance by regulating cell cycle phase distribution in mouse embryonic stem cells. Differentiation. 2011. doi: 10.1016/j.diff.2010.08.002.PubMedGoogle Scholar
  59. 59.
    Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ. Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling. J. Cell Biol. 2010;190:1079–91.CrossRefGoogle Scholar
  60. 60.
    Zheng W, Nagaraju G, Liu Z, Liu K. Functional roles of the phosphatidylinositol 3-kinases (PI3Ks) signaling in the mammalian ovary. Mol Cell Endocrinol. 2012. doi: 10.1016/j.mce.2011.05.027.Google Scholar
  61. 61.
    Barkalina N, Jones C, Wood MJ, Coward K. Extracellular vesicle-mediated delivery of molecular compounds into gametes and embryos: learning from nature. Hum Reprod Update. 2015. doi: 10.1093/humupd/dmv027.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics G. SichelUniversity of CataniaCataniaItaly

Personalised recommendations