Animal Reproduction (AR)
Animal Reproduction (AR)
Conference Paper

Contributions from the ovarian follicular environment to oocyte function

Maite del Collado, Gabriella Mamede Andrade, Flávio Vieira Meirelles, Juliano Coelho da Silveira, Felipe Perecin

Downloads: 0
Views: 536


The magnitude of oocyte’s role for embryo development is categorical. This unique cell contains the machineries and cellular components necessary to remodel male and female chromatin, to sustain early development and to, ultimately, generate a complete and complex individual. However, to gain these competences before fertilization, the oocyte undergoes several morphological, cellular and molecular changes during its lifetime enclosed in the ovarian follicle. This review will briefly revisit how the oocyte orchestrate the follicular cells, and how molecules transit to the oocyte from the innermost (cumulus) and outermost (antrum and granulosa cells) layers surrounding the follicleenclosed oocyte. Finally, we will discuss the interferences of in vitro culture conditions in the communication of the oocyte with its surrounding cells and the potential strategies to modulate these communication systems to increase oocyte competence.


cell-to-cell communication, cumulus-oocyte interactions, extracellular vesicles.


Andrade G, Meirelles F, Perecin F, da Silveira JC. 2017a. Cellular and extracellular vesicular origins of miRNAs within the bovine ovarian follicle. Reprod Domest Anim, 52:1036-1045.

Andrade GM, da Silveira JC, Perrini C, Del Collado M, Gebremedhn S, Tesfaye D, Meirelles FV, Perecin F. 2017b. The role of the PI3K-Akt signaling pathway in the developmental competence of bovine oocytes. PLoS One, 12:e0185045. doi: 10.1371/journal.pone. 0185045.

Assou S, Al-edani T, Haouzi D, Philippe N, Lecellier CH, Piquemal D, Commes T, Ait-Ahmed O, Dechaud H, Hamamah S. 2013. MicroRNAs: new candidates for the regulation of the human cumulusoocyte complex. Hum Reprod, 28:3038-3049.

Bergandi L, Basso G, Evangelista F, Canosa S, Dalmasso P, Aldieri E, Revelli A, Benedetto C. Ghigo D. 2014. Inducible Nitric Oxide Synthase and Heme Oxygenase 1 Are Expressed in Human Cumulus Cells and May Be Used as Biomarkers of Oocyte Competence. Reprod Sci, 21:1370-1377.

Biggers JD, Whittingham DG, Donahue RP. 1967. The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci U S A, 58:560-567.

Carabatsos MJ, Elvin J, Matzuk MM, Albertini DF. 1998. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol, 204:373-384.

Chang HM, Cheng JC, Taylor E, Leung PC. 2014. Oocyte-derived BMP15 but not GDF9 down-regulates connexin43 expression and decreases gap junction intercellular communication activity in immortalized human granulosa cells. Mol Hum Reprod, 20:373-383.

Chang HM, Qiao J, Leung PC. 2016. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Hum Reprod Update, 23:1-18.

Choi DS, Kim DK, Kim YK, Gho YS. 2013. Proteomics, transcriptomics and lipidomics of exosomes and ectosomes. Proteomics, 13:1554-1571.

Cillo F, Brevini TAL, Antonini S, Paffoni A, Ragni G, Gandolfi F. 2007. Association between human oocyte developmental competence and expression levels of some cumulus genes. Reproduction, 134:645-650.

Clarke H. 2017. Control of Mammalian Oocyte Development by Interactions with the Maternal Follicular Environment. Results Probl Cell Differ, 63:17-41.

Clarke HJ. 2018. Regulation of germ cell development by intercellular signaling in the mammalian ovarian follicle. Wiley Interdiscip Rev Dev Biol, 7. doi: 10.1002/wdev.294.

Combelles CMH, Carabatsos MJ, Kumar TR, Matzuk MM, Albertini DF. 2004. Hormonal control of somatic cell oocyte interactions during ovarian follicle development. Mol Reprod Dev, 69:347-355.

Conti M, Hsieh M, Zamah AM, Oh JS. 2012. Novel signaling mechanisms in the ovary during oocyte maturation and ovulation. Mol Cell Endocrinol, 356:65- 73.

da Silveira JC, Veeramachaneni DN, Winger QA, Carnevale EM, Bouma GJ. 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, 86:71.

da Silveira JC, de Andrade GM, Nogueira MFG, Meirelles FV, Perecin F. 2015. Involvement of miRNAs and Cell-Secreted Vesicles in Mammalian Ovarian Antral Follicle Development. Reprod Sci, 22:1474-1483.

da 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. 2017. Supplementation with small-extracellular vesicles from ovarian follicular fluid during in vitro production modulates bovine embryo development. PloS one, 12:e0179451.

de Loos F, van Vliet C, van Maurik P, Kruip TA. 1989. Morphology of immature bovine oocytes. Gamete Res, 24:197-204.

de Loos F, Kastrop P, Van Maurik P, Van Beneden TH, Kruip TA. 1991. Heterologous cell contacts and metabolic coupling in bovine cumulus oocyte complexes. Mol Reprod Dev, 28:255-259.

del Collado M, Saraiva NZ, Lopes FL, Gaspar RC, Padilha LC, Costa RR, Rossi GF, Vantini R, Garcia JM. 2016. Influence of bovine serum albumin and fetal bovine serum supplementation during in vitro maturation on lipid and mitochondrial behaviour in oocytes and lipid accumulation in bovine embryos. Reprod Fertil Dev, 28:1721. doi: 10.1071/RD15067.

del Collado M, da Silveira JC, Oliveira MLF, Alves BMSM, Simas CS, Godoy AT, Coelho MB, Marques LA, Carriero MM, Nogueira MFG, Eberlin MN, Silva LA, Meirelles FV, Perecin F. 2017a. In vitro maturation impacts cumulus oocyte complex metabolism and stress in cattle. Reproduction, 154:881- 893.

del Collado M, da Silveira JC, Sangalli JR, Andrade GM, Sousa L, Silva LA, Meirelles FV, Perecin F. 2017b. Fatty Acid Binding Protein 3 And Transzonal Projections Are Involved In Lipid Accumulation During In vitro Maturation Of Bovine Oocytes. Sci Rep, 7:2645.

Di Pietro C. 2016. Exosome-mediated communication in the ovarian follicle. J Assist Reprod Genet, 33:303- 311.

Dong JW, Albertini DF, Nishimori K, Kumar TR, Lu NF, Matzuk MM. 1996. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature, 383:531-535.

Edson MA, Nagaraja AK, Matzuk MM. 2009. The mammalian ovary from genesis to revelation. Endocr Rev, 30:624-712.

El-Hayek S, Yang Q, Abbassi L, FitzHarris G, Clarke HJ. 2018. Mammalian Oocytes Locally Remodel Follicular Architecture to Provide the Foundation for Germline-Soma Communication. Curr Biol, 28:1124-1131e3.

Eppig JJ. 2001. Oocyte control of ovarian follicular development and function in mammals. Reproduction, 122:829-838.

Eppig JJ, Pendola FL, Wigglesworth K, Pendola JK. 2005. Mouse oocytes regulate metabolic cooperativity between granulosa cells and oocytes: Amino acid transport. Biol Reprod, 73:351-357.

Fair T, Hyttel P, Greve T. 1995. Bovine oocyte diameter in relation to maturational competence and transcriptional activity. Mol Reprod Dev, 42:437-442.

Feuerstein P, Puard V, Chevalier C, Teusan R, Cadoret V, Guerif F, Houlgatte R, Royere D. 2012.

Genomic Assessment of Human Cumulus Cell Marker Genes as Predictors of Oocyte Developmental Competence: Impact of Various Experimental Factors. Plos One, 7:e40449.

FitzHarris G, Siyanov V, Baltz JM. 2007. Granulosa cells regulate oocyte intracellular pH against acidosis in preantral follicles by multiple mechanisms. Development, 134:4283-4295.

Fortune JE. 1994. Ovarian follicular growth and development in mammals. Biol Reprod, 50:225-232.

Fukui Y, Sakuma Y. 1980. Maturation of bovine oocytes cultured in vitro: relation to ovarian activity, follicular size and the presence or absence of cumulus cells. Biol Reprod, 22:669-673.

Gershon E, Plaks V, Dekel N. 2008. Gap junctions in the ovary: expression, localization and function. Mol Cell Endocrinol, 282:18-25.

Gilchrist RB, Thompson JG. 2007. Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro. Theriogenology, 67:6-15.

Gilchrist RB, Lane M, Thompson JG. 2008. Oocytesecreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update, 14:59-177.

Granot I, Dekel N. 2002. The ovarian gap junction protein connexin43: regulation by gonadotropins. Trends Endocrin Met, 13:310-313.

Heinzmann J, Hansmann T, Herrmann D, Wrenzycki C, Zechner U, Haaf T, Niemann H. 2011. Epigenetic profile of developmentally important genes in bovine oocytes. Mol Reprod Dev, 78:188-201.

Hung WT, Hong XA, Christenson LK, McGinnis LK. 2015. Extracellular Vesicles from Bovine Follicular Fluid Support Cumulus Expansion. Biol Reprod, 93. doi: 10.1095/biolreprod.115.132977.

Jaffe LA, Egbert JR. 2017. Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle. Annu Rev Physiol, 79:237-260.

Jiang Z, Sun J, Dong H, Luo O, Zheng X, Obergfell C, Tang Y, Bi J, O'Neill R, Ruan Y, Chen J, Tian XC. 2014. Transcriptional profiles of bovine in vivo pre-implantation development. BMC Genomics, 15:756. doi: 10.1186/1471-2164-15-756.

Jones GM, Cram DS, Song B, Magli MC, Gianaroli L, Lacham-Kaplan O, Findlay JK, Jenkin G, Trounson AO. 2008. Gene expression profiling of human oocytes following in vivo or in vitro maturation. Hum Reprod, 23:1138-1144.

Kaivo-Oja N, Bondestam J, Kamarainen M, Koskimies J, Vitt U, Cranfield M, Vuojolainen K, Kallio JP, Olkkonen VM, Hayashi M, Moustakas A, Groome NP, ten Dijke P, Hsueh AJW, Ritvos O. 2003. Growth differentiation factor-9 induces Smad2 activation and inhibin B production in cultured human granulosa-luteal cells. J Clin Endocr Metab, 88:755- 762.

Kaivo-Oja N, Mottershead DG, Mazerbourg S, Myllymaa S, Duprat S, Gilchrist RB, Groome NP, Hsueh AJ, Ritvos O. 2005. Adenoviral gene transfer allows Smad-responsive gene promoter analyses and delineation of type I receptor usage of transforming growth factor-beta family ligands in cultured human granulosa luteal cells. J Clin Endocr Metab, 90:271- 278.

Katz-Jaffe MG, McCallie BR, Preis KA, Filipovits J, Gardner DK. 2009. Transcriptome analysis of in vivo and in vitro matured bovine MII oocytes. Theriogenology, 71:939-946.

Khurana NK, Niemann H. 2000. Energy metabolism in preimplantation bovine embryos derived in vitro or in vivo. Biol Reprod, 62:847-856.

Kues WA, Sudheer S, Herrmann D, Carnwath JW, Havlicek V, Besenfelder U, Lehrach H, Adjaye J, Niemann H. 2008. Genome-wide expression profiling reveals distinct clusters of transcriptional regulation during bovine preimplantation development in vivo. Proc Natl Acad Sci U S A, 105:19768-19773.

Li HJ, Sutton-McDowall ML, Wang X, Sugimura S, Thompson JG, Gilchrist RB. 2016. Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions. Hum Reprod, 31:810- 821.

Li R, Albertini DF. 2013. The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte. Nat Rev Mol Cell Biol, 14:141-152.

Lodde V, Franciosi F, Tessaro I, Modina SC, Luciano AM. 2013. Role of gap junction-mediated communications in regulating large-scale chromatin configuration remodeling and embryonic developmental competence acquisition in fully grown bovine oocyte. J Assist Reprod Genet, 30:1219-1226.

Lodde V, Modina S, Galbusera C, Franciosi F, Luciano AM. 2007. Large-scale chromatin remodeling in germinal vesicle bovine oocytes: Interplay with gap junction functionality and developmental competence. Mol Reprod Dev, 74:740-749.

Lodde V, Modina S, Maddox-Hyttel P, Franciosi F, Lauria A, Luciano AM. 2008. Oocyte morphology and transcriptional silencing in relation to chromatin remodeling during the final phases of bovine oocyte growth. Mol Reprod Dev, 75:915-924.

Lonergan P, Monaghan P, Rizos D, Boland MP, Gordon I. 1994. Effect of Follicle Size on Bovine Oocyte Quality and Developmental Competence Following Maturation, Fertilization, and Culture inVitro. Mol Reprod Dev, 37:48-53.

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. 2016. Extracellular Vesicles from BOEC in In vitro Embryo Development and Quality. PloS one, 11: e0148083. doi: 10.1371/journal.pone.0148083.

Luciano AM, Lodde V, Beretta MS, Colleoni S, Lauria A, Modina S. 2005. Developmental capability of denuded bovine oocyte in a co-culture system with intact cumulus-oocyte complexes: role of cumulus cells, cyclic adenosine 3',5'-monophosphate, and glutathione. Mol Reprod Dev, 71:389-397.

Luciano AM, Franciosi F, Modina SC, Lodde V. 2011. Gap junction-mediated communications regulate chromatin remodeling during bovine oocyte growth and differentiation through cAMP-dependent mechanism(s). Biol Reprod, 85:1252-1259.

Luciano AM, Sirard MA. 2018. Successful in vitro maturation of oocytes: a matter of follicular differentiation. Biol Reprod, 98:162-169.

Macaulay AD, Gilbert I, Caballero J, Barreto R, Fournier E, Tossou P, Sirard MA, Clarke HJ, Khandjian EW, Richard FJ, Hyttel P, Robert C. 2014. The gametic synapse: RNA transfer to the bovine oocyte. Biol Reprod, 91:90. doi:10.1095/biolreprod.114.119867

Macaulay AD, Gilbert I, Scantland S, Fournier E, Ashkar F, Bastien A, Saadi HA, Gagne D, Sirard MA, Khandjian EW, Richard FJ, Hyttel P, Robert C. 2016. Cumulus Cell Transcripts Transit to the Bovine Oocyte in Preparation for Maturation. Biol Reprod, 94:16. doi:10.1095/biolreprod.114.127571.

Matoba S, Bender K, Fahey AG, Mamo S, Brennan L, Lonergan P, Fair T. 2014. Predictive value of bovine follicular components as markers of oocyte developmental potential. Reprod Fertil Dev, 26:337- 345.

McBride D, Carre W, Sontakke SD, Hogg CO, Law A, Donadeu FX, Clinton M. 2012. Identification of miRNAs associated with the follicular-luteal transition in the ruminant ovary. Reproduction, 144:221-233.

Moore RK, Otsuka F, Shimasaki S. 2003. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J Biol Chem, 278:304-310.

Navakanitworakul R, Hung WT, Gunewardena S, Davis JS, Chotigeat W, Christenson LK. 2016. Characterization and Small RNA Content of Extracellular Vesicles in Follicular Fluid of Developing Bovine Antral Follicles. Sci Rep, 6:25486. doi: 10.1038/srep25486.

Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang HC, Ke HM, Nikolaev VO, Jaffe LA. 2009. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development, 136:1869- 1878.

Nuttinck F, Peynot N, Humblot P, Massip A, Dessy F, Flechon JE. 2000. Comparative immunohistochemical distribution of connexin 37 and connexin 43 throughout folliculogenesis in the bovine ovary. Mol Reprod Dev, 57:60-66.

Petrocelli T, Lye SJ. 1993. Regulation of transcripts encoding the myometrial gap junction protein, connexin-43, by estrogen and progesterone. Endocrinology, 133:284-290.

Pulkki MM, Myllymaaa S, Pasternack A, Lun S, Ludlow H, Al-Qahtani A, Korchynskyi O, Groome N, Juengel JL, Kalkkinen N, Laitinen M, Ritovs O, Mottershead DG. 2011. The bioactivity of human bone morphogenetic protein-15 is sensitive to C-terminal modification: Characterization of the purified untagged processed mature region. Mol Cell Endocrinol, 332:106-115.

Raposo G, Stoorvogel W. 2013. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol, 200:373-383.

Rizos D, Fair T, Papadopoulos S, Boland MP, Lonergan P. 2002a. Developmental, qualitative, and ultrastructural differences between ovine and bovine embryos produced in vivo or in vitro. Mol Reprod Dev, 62:320-327.

Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. 2002b. 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, 61:234-248.

Robert C, Gilbert I. 2018. Cell-to-Cell Communication in the Ovarian Follicle. In book: Module in Biomedical Sciences. Elsevier, doi:10.1016/B978-0-12-801238-3.64391-X.

Russell DL, Gilchrist RB, Brown HM, Thompson JG. 2016. Bidirectional communication between cumulus cells and the oocyte: Old hands and new players? Theriogenology, 86:62-68.

Sang Q, Yao ZY, Wang H, Feng RZ, Wang HJ, Zhao XZ, Xing QH, Jin L, He L, Wu LQ, Wang L. 2013.

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, 98:3068-3079.

Santonocito M, Vento M, Guglielmino MR, Battaglia R, Wahlgren J, Ragusa M, Barbagallo D, Borzi P, Rizzari S, Maugeri M, Scollo P, Tatone C, Valadi H, Purrello M, 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-U1590.

Seidel GE. 2006. Modifying oocytes and embryos to improve their cryopreservation. Theriogenology, 65:228-235.

Sinha PB, Tesfaye D, Rings F, Hossien M, Hoelker M, Held E, Neuhoff C, Tholen E, Schellander K, Salilew-Wondim D. 2017. MicroRNA-130b is involved in bovine granulosa and cumulus cells function, oocyte maturation and blastocyst formation. J Ovarian Res, 10:37. doi: 10.1186/s13048-017-0336-1.

Sirard MA, Richard F, Mayes M. 1998. Controlling meiotic resumption in bovine oocytes: A review. Theriogenology, 49:483-497.

Sohel MMH, Hoelker M, Noferesti SS, SalilewWondim D, Tholen E, Looft C, Rings F, Uddin MJ, Spencer TE, Schellander K, Tesfaye D. 2013.

Exosomal and Non-Exosomal Transport of ExtraCellular microRNAs in Follicular Fluid: Implications for Bovine Oocyte Developmental Competence. PLoS One, 8:e78505. doi: 10.1371/journal.pone.0078505.

Sugimura S, Yamanouchi T, Palmerini MG, Hashiyada Y, Imai K, Gilchrist RB. 2018. Effect of pre-in vitro maturation with cAMP modulators on the acquisition of oocyte developmental competence in cattle. J Reprod Dev, 64:233-241.

Sugiura K, Eppig JJ. 2005. Society for Reproductive Biology Founders' Lecture 2005 - Control of metabolic cooperativity between oocytes and their companion granulosa cells by mouse oocytes. Reprod Fert Dev, 17:667-674.

Sutton ML, Cetica PD, Beconi MT, Kind KL, Gilchrist RB, Thompson JG. 2003a. Influence of oocyte-secreted factors and culture duration on the metabolic activity of bovine cumulus cell complexes. Reproduction, 126:27-34.

Sutton ML, Gilchrist RB, Thompson JG. 2003b. Effects of in-vivo and in-vitro environments on the metabolism of the cumulus-oocyte complex and its influence on oocyte developmental capacity. Hum Reprod Update, 9:35-48.

Sutton-McDowall ML, Gilchrist RB, Thompson JG. 2010. The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction, 139:685-695.

Thomas RE, Armstrong DT, Gilchrist RB. 2004a. Bovine cumulus cell-oocyte gap junctional communication during in vitro maturation in response to manipulation of cell-specific cyclic adenosine 3',5'- monophosophate levels. Biol Reprod, 70:548-556.

Thomas RE, Thompson JG, Armstrong DT, Gilchrist RB. 2004b. Effect of specific phosphodiesterase isoenzyme inhibitors during in vitro maturation of bovine oocytes on meiotic and developmental capacity. Biol Reprod, 71:1142-1149.

Vaccari S, Weeks JL, Hsieh M, Menniti FS, Conti M. 2009. Cyclic GMP Signaling Is Involved in the Luteinizing Hormone-Dependent Meiotic Maturation of Mouse Oocytes. Biol Reprod, 81:595-604.

Yan C, Wang P, DeMayo J, DeMayo FJ, Elvin JA, Carino C, Prasad SV, Skinner SS, Dunbar BS, Dube JL, Celeste AJ, Matzuk MM. 2001. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol, 15:854-866.

Yuan Y, Ida JM, Paczkowski M, Krisher RL. 2011. Identification of Developmental Competence-Related Genes in Mature Porcine Oocytes. Mol Reprod Dev, 78:565-575.

Zhang L, Jiang S, Wozniak PJ, Yang X, Godke RA. 1995. Cumulus cell function during bovine oocyte maturation, fertilization, and embryo development in vitro. Mol Reprod Dev, 40:338-344.

5b76c3be0e8825096c8068a7 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections