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Influence of Extracellular Vesicles from the Follicular Fluid of Young Women and Women of Advanced Maternal Age with Different miRNA Profiles on Sperm Functional Properties

  • Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

We studied the effect of co-culturing of extracellular vesicles in the follicular fluid of young women and women of advanced maternal age on sperm motility. Vesicles were obtained by differential centrifugation. The sperm fraction was isolated from the seminal fluid of 18 patients (age 28-36 years). The spermatozoa were incubated with vesicles (1:2 ratio) for 60 or 120 min at 37°C in a CO2 incubator. A fraction of spermatozoa incubated without vesicles served as the control. After the incubation, the sperm samples were sedimented by centrifugation, fixed in 2.5% glutaraldehyde, and analyzed by transmission electron microscopy. RNA was isolated from the follicular fluid vesicles by column method followed by cDNA synthesis in a reaction mixture according to miScript II RT Kit protocol (Qiagen). After 60-min incubation with extracellular vesicles from the follicular fluid of women of advanced maternal age, the sperm motility and hyperactivation slightly changed in comparison with the group where incubation was performed with follicular fluid vesicles from young women and control group. Follicular fluid miRNA profiles in women of different ages varied, which suggests different functional compositions and effects of follicular fluid vesicles of different age groups on sperm characteristics. Transmission electron microscopy revealed differences in the interaction of follicular fluid vesicles from women of different age groups with spermatozoa. Further study of the effect of extracellular vesicles from the follicular fluid and analysis of their transcriptomic, proteomic, and metabolomic composition on sperm mobility and fertilizing ability will improve the effectiveness of assisted reproductive technology programs in patients with male infertility.

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References

  1. Almiñana C, Corbin E, Tsikis G, Alcântara-Neto AS, Labas V, Reynaud K, Galio L, Uzbekov R, Garanina AS, Druart X, Mermillod P. Oviduct extracellular vesicles protein content and their role during oviduct-embryo cross-talk. Reproduction. 2017;154(3):153-168. https://doi.org/10.1530/REP-17-0054

    Article  PubMed  Google Scholar 

  2. Alonso CAI, Osycka-Salut CE, Castellano L, Cesari A, Di Siervi N, Mutto A, Johannisson A, Morrell JM, Davio C, Perez-Martinez S. Extracellular cAMP activates molecular signalling pathways associated with sperm capacitation in bovines. Mol. Hum. Reprod. 2017;23(8):521-534. https://doi.org/10.1093/molehr/gax030

    Article  CAS  PubMed  Google Scholar 

  3. Andronico F, Battaglia R, Ragusa M, Barbagallo D, Purrello M, Di Pietro C. Extracellular vesicles in human oogenesis and implantation. Int. J. Mol. Sci. 2019;20(9):2162. https://doi.org/10.3390/ijms20092162

    Article  CAS  PubMed Central  Google Scholar 

  4. Babayev E, Duncan FE. Age-associated changes in cumulus cells and follicular fluid: the local oocyte microenvironment as a determinant of gamete quality. Biol. Reprod. 2022;106(2):351-365. https://doi.org/10.1093/biolre/ioab241

    Article  PubMed  Google Scholar 

  5. Battaglia R, Musumeci P, Ragusa M, Barbagallo D, Scalia M, Zimbone M, Lo Faro JM, Borzì P, Scollo P, Purrello M, Vento EM, Di Pietro C. Ovarian aging increases small extracellular vesicle CD81+ release in human follicular fluid and influences miRNA profiles. Aging (Albany NY). 2020;12(12):12324-12341. https://doi.org/10.18632/aging.103441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chaves BR, Pinoti Pavaneli AP, Blanco-Prieto O, Pinart E, Bonet S, Zangeronimo MG, Rodríguez-Gil JE, Yeste M. Exogenous albumin is crucial for pig sperm to elicit in vitro capacitation whereas bicarbonate only modulates its efficiency. Biology (Basel). 2021;10(11):1105. https://doi.org/10.3390/biology10111105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chen B, Xu P, Wang J, Zhang C. The role of MiRNA in polycystic ovary syndrome (PCOS). Gene. 2019;706:91-96. https://doi.org/10.1016/j.gene.2019.04.082

    Article  CAS  PubMed  Google Scholar 

  8. Di Pietro C. Exosome-mediated communication in the ovarian follicle. J. Assist. Reprod. Genet. 2016;33(3):303-311. https://doi.org/10.1007/s10815-016-0657-9

    Article  PubMed  PubMed Central  Google Scholar 

  9. Diez-Fraile A, Lammens T, Tilleman K, Witkowski W, Verhasselt B, De Sutter P, Benoit Y, Espeel M, D’Herde K. Age-associated differential microRNA levels in human follicular fluid reveal pathways potentially determining fertility and success of in vitro fertilization. Hum. Fertil (Camb). 2014;17(2):90-98. https://doi.org/10.3109/14647273.2014.897006

    Article  CAS  PubMed  Google Scholar 

  10. DePaolo LV. Age-associated increases in serum follicle-stimulating hormone levels on estrus are accompanied by a reduction in the ovarian secretion of inhibin. Exp. Aging Res. 1987;13(1-2):3-7. https://doi.org/10.1080/03610738708259293

    Article  CAS  PubMed  Google Scholar 

  11. Ferraz MAMM, Carothers A, Dahal R, Noonan MJ, Songsasen N. Oviductal extracellular vesicles interact with the spermatozoon’s head and mid-piece and improves its motility and fertilizing ability in the domestic cat. Sci. Rep. 2019;9(1):9484. https://doi.org/10.1038/s41598-019-45857-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hackl M, Brunner S, Fortschegger K, Schreiner C, Micutkova L, Mück C, Laschober GT, Lepperdinger G, Sampson N, Berger P, Herndler-Brandstetter D, Wieser M, Kühnel H, Strasser A, Rinnerthaler M, Breitenbach M, Mildner M, Eckhart L, Tschachler E, Trost A, Bauer JW, Papak C, Trajanoski Z, Scheideler M, Grillari-Voglauer R, Grubeck-Loebenstein B, Jansen-Dürr P, Grillari J. miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell. 2010;9(2):291-296. https://doi.org/10.1111/j.1474-9726.2010.00549.x

    Article  CAS  PubMed  Google Scholar 

  13. Hasan MM, Reshi QUA, Lättekivi F, Viil J, Godakumara K, Dissanayake K, Andronowska A, Jaakma Ü, Fazeli A. Bovine follicular fluid derived extracellular vesicles modulate the viability, capacitation and acrosome reaction of bull spermatozoa. Biology (Basel). 2021;10(11):1154. https://doi.org/10.3390/biology10111154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jung HJ, Suh Y. Circulating miRNAs in ageing and ageing-related diseases.J. Genet. Genomics. 2014;41(9):465-472. https://doi.org/10.1016/j.jgg.2014.07.003

    Article  Google Scholar 

  15. Kenigsberg S, Wyse BA, Librach CL, da Silveira JC. Protocol for exosome isolation from small volume of ovarian follicular fluid: evaluation of ultracentrifugation and commercial kits. Methods Mol. Biol. 2017;1660:321-341. https://doi.org/10.1007/978-1-4939-7253-1_26

    Article  CAS  PubMed  Google Scholar 

  16. Keyser S, van der Horst G, Maree L. Progesterone, myo-inositol, dopamine and prolactin present in follicular fluid have differential effects on sperm motility subpopulations. Life (Basel). 2021;11(11):1250. https://doi.org/10.3390/life11111250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217. https://doi.org/10.1016/j.cell.2013.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Marín-Briggiler CI, Luque GM, Gervasi MG, Oscoz-Susino N, Sierra JM, Mondillo C, Salicioni AM, Krapf D, Visconti PE, Buffone MG. Human sperm remain motile after a temporary energy restriction but do not undergo capacitation-related events. Front. Cell Dev. Biol. 2021;9:777086. https://doi.org/10.3389/fcell.2021.777086

    Article  PubMed  PubMed Central  Google Scholar 

  19. Martinez RM, Liang L, Racowsky C, Dioni L, Mansur A, Adir M, Bollati V, Baccarelli AA, Hauser R, Machtinger R. Extracellular microRNAs profile in human follicular fluid and IVF outcomes. Sci. Rep. 2018;8(1):17036. https://doi.org/10.1038/s41598-018-35379-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Moreno JM, Núñez MJ, Quiñonero A, Martínez S, de la Orden M, Simón C, Pellicer A, Díaz-García C, Domínguez F. 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;104(4):1037-1046.e1. https://doi.org/10.1016/j.fertnstert.2015.07.001

    Article  CAS  PubMed  Google Scholar 

  21. Pocate-Cheriet K, Santulli P, Kateb F, Bourdon M, Maignien C, Batteux F, Chouzenoux S, Patrat C, Wolf JP, Bertho G, Chapron C. The follicular fluid metabolome differs according to the endometriosis phenotype. Reprod. Biomed. Online. 2020;41(6):1023-1037. https://doi.org/10.1016/j.rbmo.2020.09.002

    Article  CAS  PubMed  Google Scholar 

  22. Qasemi M, Amidi F. Extracellular microRNA profiling in human follicular fluid: new biomarkers in female reproductive potential. J. Assist. Reprod. Genet. 2020;37(8):1769-1780. https://doi.org/10.1007/s10815-020-01860-0

    Article  PubMed  PubMed Central  Google Scholar 

  23. Scalici E, Traver S, Mullet T, Molinari N, Ferrières A, Brunet C, Belloc S, Hamamah S. Circulating microRNAs in follicular fluid, powerful tools to explore in vitro fertilization process. Sci. Rep. 2016;6:24976. https://doi.org/10.1038/srep24976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Serafini S, O’Flaherty C. Redox Regulation to Modulate Phosphorylation Events in Human Spermatozoa.Antioxid. Redox Signal. 2021. Dec 15. https://doi.org/10.1089/ars.2021.0117

  25. Sohel MM, Hoelker M, Noferesti SS, Salilew-Wondim D, Tholen E, Looft C, Rings F, Uddin MJ, Spencer TE, Schellander K, Tesfaye D. Exosomal and non-exosomal transport of extra-cellular microRNAs in follicular fluid: implications for bovine oocyte developmental competence. PLoS One. 2013;8(11):e78505. https://doi.org/10.1371/journal.pone.0078505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sysoeva AP, Makarova NP, Silachev DN, Lobanova NN, Shevtsova YA, Bragina EE, Kalinina EA, Sukhikh GT. Influence of extracellular vesicles of the follicular fluid on morphofunctional characteristics of human sperm. Bull. Exp. Biol. Med. 2021;172(2):254-262. https://doi.org/10.1007/s10517-021-05372-4

    Article  CAS  PubMed  Google Scholar 

  27. Zhang D, Lv J, Tang R, Feng Y, Zhao Y, Fei X, Chian R, Xie Q. Association of exosomal microRNAs in human ovarian follicular fluid with oocyte quality. Biochem. Biophys. Res. Commun. 2021;534:468-473. https://doi.org/10.1016/j.bbrc.2020.11.058

    Article  CAS  PubMed  Google Scholar 

  28. Zhang X, Song D, Kang H, Zhou W, Chen H, Zeng X. Seminal plasma exosomes evoke calcium signals via the CatSper channel to regulate human sperm function. BioRxiv. 2020. https://doi.org/10.1101/2020.05.21.094433

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Correspondence to A. P. Sysoeva.

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Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 117-126, June, 2022

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Sysoeva, A.P., Nepsha, O.S., Makarova, N.P. et al. Influence of Extracellular Vesicles from the Follicular Fluid of Young Women and Women of Advanced Maternal Age with Different miRNA Profiles on Sperm Functional Properties. Bull Exp Biol Med 173, 560–568 (2022). https://doi.org/10.1007/s10517-022-05589-x

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