Animal Reproduction (AR)
Animal Reproduction (AR)

The role of the oviduct and extracellular vesicles during early embryo development in bovine

Natália Marins Bastos; Juliana Germano Ferst; Rodrigo Silva Goulart; Juliano Coelho da Silveira

Downloads: 0
Views: 64


The oviduct is an important reproductive structure that connects the ovary to the uterus and takes place to important events such as oocyte final maturation, fertilization and early embryonic development. Thus, gametes and embryo can be directly influenced by the oviductal microenvironment composed by epithelial cells such secretory and ciliated cells and oviductal fluid. The oviduct composition is anatomically dynamic and is under ovarian hormones control. The oviductal fluid provides protection, nourishment and transport to gametes and embryo and allows interaction to oviductal epithelial cells. All these functions together allows the oviduct to provides the ideal environment to the early reproductive events. Extracellular vesicles (EVs) are biological nanoparticles that mediates cell communication and are present at oviductal fluid and plays an important role in gametes/embryo - oviductal cells communication. This review will present the ability of the oviducts based on its dynamic and systemic changes during reproductive events, as well as the contribution of EVs in this process.


oviductal environment, oviductal fluid, cell communication


Al-Dossary AA, Martin-DeLeon PA. Role of exosomes in the reproductive tract Oviductosomes mediate interactions of oviductal secretion with gametes early embryo. Front Biosci. 2016;21(6):1278. PMid:27100506.

Al-Dossary AA, Strehler EE, Martin-DeLeon PA. Expression and secretion of plasma membrane Ca2+-ATPase 4a (PMCA4a) during murine estrus: association with oviductal exosomes and uptake in sperm. PLoS One. 2013;8(11):e80181. PMid:24244642.

Almiñana C, Bauersachs S. Extracellular vesicles: multi-signal messengers in the gametes/embryo-oviduct cross-talk. Theriogenology. 2020;150:59-69. PMid:32088033.

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):153-68. PMid:28630101.

Almiñana C, Tsikis G, Labas V, Uzbekov R, Silveira JC, Bauersachs S, Mermillod P. Deciphering the oviductal extracellular vesicles content across the estrous cycle: implications for the gametes-oviduct interactions and the environment of the potential embryo. BMC Genomics. 2018;19(1):622. PMid:30134841.

Amini MR, Kohram H, Zare Shahaneh A, Zhandi M, Sharideh H, Nabi MM. The effects of different levels of vitamin E and vitamin C in modified Beltsville extender on rooster post-thawed sperm quality. Cell Tissue Bank. 2015;16(4):587-92. PMid:25779925.

Aplin JD. Implantation. In: Henry HL, Norman AW, editors. Encyclopedia of hormones. Amsterdam: Academic Press; 2003. p. 289-97.

Avilés M, Coy P, Rizos D. The oviduct : a key organ for the success of early reproductive events. Anim Front. 2015;5(1):25-31.

Banliat C, Le Bourhis D, Bernardi O, Tomas D, Labas V, Salvetti P, Guyonnet B, Mermillod P, Saint-Dizier M. Oviduct fluid extracellular vesicles change the phospholipid composition of bovine embryos developed in vitro. Int J Mol Sci. 2020;21(15):1-13. PMid:32727074.

Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136(2):215-33. PMid:19167326.

Bartel DP. Metazoan MicroRNAs. Cell. 2018;173(1):20-51. PMid:29570994.

Battaglia R, Palin S, Vento ME, Ferlita AL, Faro MJL, Caroppo E, Borzi P, Falzone L, Barbagallo D, Ragusa M, Scalia M, D'Amato G, Scollo P, Musumeci P, Purrello M, Gravotta E, Di Pietro C. Identification of extracellular vesicles and characterization of miRNA expression profiles in human blastocoel fluid. Sci Rep. 2019;1–11. 10.1038/s41598-018-36452-7.

Bauersachs S, Almiñana C. Embryo–maternal interactions underlying reproduction in mammals. Int J Mol Sci. 2020;21(14):1-6. PMid:32664189.

Beier HM. Oviducal and uterine fluids. J Reprod Fertil. 1974;37(1):221-37. PMid:4593606.

Besenfelder U, Brem G, Havlicek V. Review : environmental impact on early embryonic development in the bovine species. Animal. 2020;14(S1):103-12. PMid:32024564.

Besenfelder U, Havlicek V, Brem G. Role of the oviduct in early embryo development. Reprod Domest Anim. 2012;47(Suppl. 4):156-63. PMid:22827365.

Binelli M, Gonella-Diaza A, Mesquita F, Membrive C. Sex steroid-mediated control of oviductal function in cattle. Biology. 2018;7(1):15. PMid:29393864.

Coy P, García-Vázquez FA, Visconti PE, Avilés M. Roles of oviduct in mammalian fertilization. Reproduction. 2012;144(6):649-60. PMid:23028122.

Dissanayake K, Nõmm M, Lättekivi F, Ressaissi Y, Godakumara K, Lavrits A, Midekessa G, Viil J, Bæk R, Jørgensen MM, Bhattacharjee S, Andronowska A, Salumets A, Jaakma Ü, Fazeli A. Individually cultured bovine embryos produce extracellular vesicles that have the potential to be used as non-invasive embryo quality markers. Theriogenology. 2020;149:104-16. PMid:32259747.

Fernandes CCL, Rodriguez-Villamil P, Vasconcelos FR, Nagano CS, Rossetto R, Moura AAAN, Rondina D. Proteome of the periovulatory oviduct and uterus of goats as related to nutritional balance. Reprod Domest Anim. 2018;53(5):1085-95. PMid:29885005.

Freeman DA, Weber JA, Geary RT, Woods GL. Time of embryo transport through the mare oviduct. Theriogenology. 1991;36(5):823-30. PMid:16727051.

Fu B, Ma H, Liu D. Extracellular vesicles function as bioactive molecular transmitters in the mammalian oviduct: an inspiration for optimizing in vitro culture systems and improving delivery of exogenous nucleic acids during preimplantation embryonic development. Int J Mol Sci. 2020;21(6):2189. PMid:32235756.

Gebert LFR, Macrae IJ. Regulation of microRNA function in animals. Nat Rev Mol Cell Biol. 2019;20:21-37. PMid:30108335.

Gonella-Diaza AM, Mesquita FS, Lopes E, Silva KR, Cogliati B, Francisco Strefezzi R, Binelli M. Sex steroids drive the remodeling of oviductal extracellular matrix in cattle. Biol Reprod. 2018;99(3):590-9. PMid:29659700.

Gonella-Diaza AM, Mesquita FS, Silva KR, Carvalho Balieiro JC, Santos NP, Pugliesi G, Strefezzi RDF. Sex steroids modulate morphological and functional features of the bovine oviduct. Cell Tissue Res. 2017;370(2):319-33. PMid:28770380.

Griffiths GS, Miller KA, Galileo DS, Martin-DeLeon PA. Murine SPAM1 is secreted by the estrous uterus and oviduct in a form that can bind to sperm during capacitation: acquisition enhances hyaluronic acid-binding ability and cumulus dispersal efficiency. Reproduction. 2008;135(3):293-301. PMid:18299422.

Gross N, Kropp J, Khatib H. MicroRNA signaling in embryo development. Biology. 2017;6(3):34. PMid:28906477.

Hamdi M, Cañon‐Beltrán K, Mazzarella R, Cajas YN, Leal CLV, Gutierrez‐Adan A, Silveira JC, Rizos D. Characterization and profiling analysis of bovine oviduct and uterine extracellular vesicles and their miRNA cargo through the estrous cycle. FASEB J. 2021;35(12):e22000. PMid:34731497.

Harris EA, Stephens KK, Winuthayanon W. Extracellular vesicles and the oviduct function. Int J Mol Sci. 2020;21:1-20. PMid:33167378.

Harvey AJ. Mitochondria in early development: linking the microenvironment, metabolism and the epigenome. Reproduction. 2019;157(5):R159-79. PMid:30870807.

Hawk HW. Sperm survival and transport in the female reproductive tract. J Dairy Sci. 1983;66(12):2645-60. PMid:6365994.

Hayashi K, Chuva de Sousa Lopes SM, Kaneda M, Tang F, Hajkova P, Lao K, O’Carroll D, Das PP, Tarakhovsky A, Miska EA, Surani MA. MicroRNA biogenesis is required for mouse primordial germ cell development and spermatogenesis. PLoS One. 2008;3(3):e1738. PMid:18320056.

Hu K, Yu Y. Metabolite availability as a window to view the early embryo microenvironment in vivo. Mol Reprod Dev. 2017;84(10):1027-38. PMid:28722155.

Huang N, Liu B, Dong Z, Mao W, Zhang N, Li C, Cao J. Prostanoid receptors EP2, EP4, and FP are regulated by estradiol in bovine oviductal smooth muscle. Prostaglandins Other Lipid Mediat. 2015;121(Pt B):170-5. PMid:26319698.

Jansen S, Cashman K, Thompson JG, Pantaleon M, Kaye PL. Glucose deprivation, oxidative stress and peroxisome proliferator-activated receptor-alpha (PPARA) cause peroxisome proliferation in preimplantation mouse embryos". Reproduction. 2009;138(3):493-505. PMid:19531609.

Kavanaugh JF, Killian GJ. Bovine oviductal cannulations. J Invest Surg. 1988;1(3):201-8. PMid:3154098.

Kölle S, Dubielzig S, Reese S, Wehrend A, König P, Kummer W. Ciliary transport, gamete interaction, and effects of the early embryo in the oviduct : ex vivo analyses using a new digital videomicroscopic system in the cow 1. Biol Reprod. 2009;81(2):267-74. PMid:19299315.

Lapointe J, Kimmins S, MacLaren LA, Bilodeau JF. Estrogen selectively up-regulates the phospholipid hydroperoxide glutathione peroxidase in the oviducts. Endocrinology. 2005;146(6):2583-92. PMid:15746255.

Lawson C, Kovacs D, Finding E, Ulfelder E, Luis-Fuentes V. Extracellular vesicles: evolutionarily conserved mediators of intercellular communication. Yale J Biol Med. 2017;90(3):481-91. PMid:28955186.

Leese HJ. Quiet please, do not disturb: a hypothesis of embryo metabolism and viability. BioEssays. 2002;24(9):845-9. PMid:12210521.

Leese HJ, Tay JI, Reischl J, Downing SJ. Formation of Fallopian tubal fluid : role of a neglected epithelium. Reproduction. 2001;121(3):339-46. PMid:11226059.

Li S, Winuthayanon W. Oviduct : roles in fertilization and early embryo development. J Endocrinol. 2017;232(1):R1-26. PMid:27875265.

Lindblom B, Hamberger L, Ljung B. Contractile patterns of isolated oviductal smooth muscle under different hormonal conditions. Fertil Steril. 1980;33(3):283-7. PMid:7364061.

Lopera-Vasquez R, Hamdi M, Fernandez-Fuertes B, Maillo V, Beltran-Brena P, Calle A, Redruello A, Lopez-Martin S, Gutierrez-Adan A, Yanez-Mo M, Ramirez MA, Rizos D. Extracellular vesicles from BOEC in in vitro embryo development and quality. PLoS One. 2016;11(2):1-23. PMid:26845570.

Machtinger R, Laurent LC, Baccarelli AA. Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update. 2016;22(2):182-93. PMid:26663221.

Mazzarella R, Bastos NM, Bridi A, del Collado M, Andrade GM, Pinzon J, Prado CM, Silva LA, Meirelles FV, Pugliesi G, Perecin F, Silveira JC. Changes in oviductal cells and small extracellular vesicles miRNAs in pregnant cows. Front Vet Sci. 2021;8:639752. PMid:33748215.

Memili E, First NL. Zygotic and embryonic gene expression in cow : a review of timing and mechanisms of early gene expression as compared with other species. Zygote. 2000;8(1):87-96. PMid:10840878.

Miki K, Clapham DE. Rheotaxis guides mammalian sperm. Curr Biol. 2013;23(6):443-52. PMid:23453951.

van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19(4):213-28. PMid:29339798.

Olsen SL, Li S, Winuthayanon W, States U. Embryo transport. In: Skinner MK, editor. Encyclopedia of reproduction. 2nd ed. Amsterdam: Elsevier; 2018. (vol. I).

Pantaleon M, Scott J, Kaye PL. Nutrient sensing by the early mouse embryo : hexosamine biosynthesis and glucose signaling during preimplantation development. Biol Reprod. 2007;78(4):595-600. PMid:18046015.

Potts DM, Wilson IB. The preimplantation conceptus of the mouse at 90 hours post coitum. J Anat. 1967;102(Pt 1):1-11. PMid:17103504.

Rizos D, Fair T, Papadopoulos S, Boland MP, Lonergan P. Developmental, qualitative, and ultrastructural differences between ovine and bovine embryos produced in vivo or in vitro. Mol Reprod Dev. 2002a;62(3):320-7. PMid:12112595.

Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Mol Reprod Dev. 2002b;61(2):234-48. PMid:11803560.

Rodríguez-Alonso B, Maillo V, Acuña OS, López-úbeda R, Torrecillas A, Simintiras CA, Sturmey R, Avilés M, Lonergan P, Rizos D. Spatial and pregnancy-related changes in the protein, amino acid, and carbohydrate composition of bovine oviduct fluid. Int J Mol Sci. 2020a;21(5):1-19. PMid:32121434.

Rodríguez-Alonso B, Sánchez JM, González E, Lonergan P, Rizos D. Challenges in studying preimplantation embryo-maternal interaction in cattle. Theriogenology. 2020b;150:139-49. PMid:31973965.

Saint-Dizier M, Schoen J, Chen S, Banliat C, Mermillod P. Composing the early embryonic microenvironment: physiology and regulation of oviductal secretions. Int J Mol Sci. 2020;21(1):1-21. PMid:31905654.

Silveira JC, Andrade GM, del Collado M, Sampaio RV, Sangalli JR, Silva LA, Pinaffi FVL, Jardim IB, Cesar MC, Nogueira MFG, Cesar ASM, Coutinho LL, Pereira RW, Perecin F, Meirelles FV. Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development. PLoS One. 2017;12(6):1-25. PMid:28617821.

Silveira JC, Andrade GM, Nogueira MFG, Meirelles FV, Perecin F. Involvement of miRNAs and cell-secreted vesicles in mammalian ovarian antral follicle development. Reprod Sci. 2015;22(12):1474-83. PMid:25736328.

Silveira JC, Ávila ACFCM, Garrett HL, Bruemmer JE, Winger QA, Bouma GJ. Cell-secreted vesicles containing microRNAs as regulators of gamete maturation. J Endocrinol. 2018;236(1):R15-27. PMid:28870888.

Suarez SS. Regulation of sperm storage and movement in the mammalian oviduct. Int J Dev Biol. 2008;52(5–6):455-62. PMid:18649258.

Tesfaye D, Hailay T, Salilew-wondim D, Hoelker M, Bitseha S, Gebremedhn S. Theriogenology extracellular vesicle mediated molecular signaling in ovarian follicle : implication for oocyte developmental competence. Theriogenology. 2020;150:70-4.

Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, Ayre DC, Bach JM, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer NN, Baxter AA, Bebawy M, Beckham C, Bedina Zavec A, Benmoussa A, Berardi AC, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borràs FE, Bosch S, Boulanger CM, Breakefield X, Breglio AM, Brennan MÁ, Brigstock DR, Brisson A, Broekman ML, Bromberg JF, Bryl-Górecka P, Buch S, Buck AH, Burger D, Busatto S, Buschmann D, Bussolati B, Buzás EI, Byrd JB, Camussi G, Carter DR, Caruso S, Chamley LW, Chang YT, Chen C, Chen S, Cheng L, Chin AR, Clayton A, Clerici SP, Cocks A, Cocucci E, Coffey RJ, Cordeiro-da-Silva A, Couch Y, Coumans FA, Coyle B, Crescitelli R, Criado MF, D’Souza-Schorey C, Das S, Datta Chaudhuri A, de Candia P, De Santana EF, De Wever O, Del Portillo HA, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich LC, Dolo V, Dominguez Rubio AP, Dominici M, Dourado MR, Driedonks TA, Duarte FV, Duncan HM, Eichenberger RM, Ekström K, El Andaloussi S, Elie-Caille C, Erdbrügger U, Falcón-Pérez JM, Fatima F, Fish JE, Flores-Bellver M, Försönits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gámez-Valero A, Gardiner C, Gärtner K, Gaudin R, Gho YS, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan DC, Görgens A, Gorski SM, Greening DW, Gross JC, Gualerzi A, Gupta GN, Gustafson D, Handberg A, Haraszti RA, Harrison P, Hegyesi H, Hendrix A, Hill AF, Hochberg FH, Hoffmann KF, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim AG, Ikezu T, Inal JM, Isin M, Ivanova A, Jackson HK, Jacobsen S, Jay SM, Jayachandran M, Jenster G, Jiang L, Johnson SM, Jones JC, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano SI, Kaur S, Kawamura Y, Keller ET, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim KP, Kislinger T, Klingeborn M, Klinke DJ 2nd, Kornek M, Kosanović MM, Kovács ÁF, Krämer-Albers EM, Krasemann S, Krause M, Kurochkin IV, Kusuma GD, Kuypers S, Laitinen S, Langevin SM, Languino LR, Lannigan J, Lässer C, Laurent LC, Lavieu G, Lázaro-Ibáñez E, Le Lay S, Lee MS, Lee YXF, Lemos DS, Lenassi M, Leszczynska A, Li IT, Liao K, Libregts SF, Ligeti E, Lim R, Lim SK, Linē A, Linnemannstöns K, Llorente A, Lombard CA, Lorenowicz MJ, Lörincz ÁM, Lötvall J, Lovett J, Lowry MC, Loyer X, Lu Q, Lukomska B, Lunavat TR, Maas SL, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova ES, Martin-Jaular L, Martinez MC, Martins VR, Mathieu M, Mathivanan S, Maugeri M, McGinnis LK, McVey MJ, Meckes DG Jr, Meehan KL, Mertens I, Minciacchi VR, Möller A, Møller Jørgensen M, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth DC, Myburgh KH, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan JP, Nolte-’t Hoen EN, Noren Hooten N, O’Driscoll L, O’Grady T, O’Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz LA, Osteikoetxea X, Østergaard O, Ostrowski M, Park J, Pegtel DM, Peinado H, Perut F, Pfaffl MW, Phinney DG, Pieters BC, Pink RC, Pisetsky DS, Pogge von Strandmann E, Polakovicova I, Poon IK, Powell BH, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai RL, Raimondo S, Rak J, Ramirez MI, Raposo G, Rayyan MS, Regev-Rudzki N, Ricklefs FL, Robbins PD, Roberts DD, Rodrigues SC, Rohde E, Rome S, Rouschop KM, Rughetti A, Russell AE, Saá P, Sahoo S, Salas-Huenuleo E, Sánchez C, Saugstad JA, Saul MJ, Schiffelers RM, Schneider R, Schøyen TH, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke GV, Shetty AK, Shiba K, Siljander PR, Silva AM, Skowronek A, Snyder OL 2nd, Soares RP, Sódar BW, Soekmadji C, Sotillo J, Stahl PD, Stoorvogel W, Stott SL, Strasser EF, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh WS, Tomasini R, Torrecilhas AC, Tosar JP, Toxavidis V, Urbanelli L, Vader P, van Balkom BW, van der Grein SG, Van Deun J, van Herwijnen MJ, Van Keuren-Jensen K, van Niel G, van Royen ME, van Wijnen AJ, Vasconcelos MH, Vechetti IJ Jr, Veit TD, Vella LJ, Velot É, Verweij FJ, Vestad B, Viñas JL, Visnovitz T, Vukman KV, Wahlgren J, Watson DC, Wauben MH, Weaver A, Webber JP, Weber V, Wehman AM, Weiss DJ, Welsh JA, Wendt S, Wheelock AM, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yáñez-Mó M, Yin H, Yuana Y, Zappulli V, Zarubova J, Žėkas V, Zhang JY, Zhao Z, Zheng L, Zheutlin AR, Zickler AM, Zimmermann P, Zivkovic AM, Zocco D, Zuba-Surma EK. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750. PMid:30637094.

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(6):654-9. PMid:17486113.

Valle GR, Cassali GD, Nogueira JC, Castro ACS, Reis AM, Cardoso FM, Figueiredo CBO, Nascimento EF. Nuclear estrogen and progesterone receptors in the oviduct of heifers under natural and superovulated estrous cycles. Anim Reprod Sci. 2007;101(1-2):28-37. PMid:17010540.

Submitted date:

Accepted date:

62588755a953950d315f8383 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections