Exosomal regulation is intimately involved in key cellular processes, such as migration, proliferation, and adhesion. By participating in the regulation of basic mechanisms, extracellular vesicles are important in intercellular signaling and the functioning of the mammalian reproductive system. The complexity of intercellular interactions in the ovarian follicle is also based on multilevel intercellular signaling, including the mechanisms involving cadherins, integrins, and the extracellular matrix. The processes in the ovary leading to the formation of a fertilization-ready oocyte are extremely complex at the molecular level and depend on the oocyte's ongoing relationship with granulosa cells. An analysis of gene expression from material obtained from a primary in vitro culture of porcine granulosa cells was employed using microarray technology. Genes with the highest expression (LIPG, HSD3B1, CLIP4, LOX, ANKRD1, FMOD, SHAS2, TAGLN, ITGA8, MXRA5, and NEXN) and the lowest expression levels (DAPL1, HSD17B1, SNX31, FST, NEBL, CXCL10, RGS2, MAL2, IHH, and TRIB2) were selected for further analysis. The gene expression results obtained from the microarrays were validated using quantitative RT-qPCR. Exosomes may play important roles regarding intercellular signaling between granulosa cells. Therefore, exosomes may have significant applications in regenerative medicine, targeted therapy, and assisted reproduction technologies.

Center of Assisted Reproduction Department of Obstetrics and Gynecology University Hospital and Masaryk University 601 77 Brno Czech Republic

Department of Anatomy Poznan University of Medical Sciences 61 701 Poznan Poland

Department of Basic and Preclinical Sciences Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Torun Poland

Department of Diagnostics and Clinical Sciences Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Torun Poland

Department of Toxicology Poznan University of Medical Sciences 61 701 Poznan Poland

Department of Veterinary Surgery Institute of Veterinary Medicine Nicolaus Copernicus University in Torun 87 100 Torun Poland

Division of Anatomy Department of Human Morphology and Embryology Wroclaw Medical University 50 367 Wroclaw Poland

Physiology Graduate Faculty College of Agriculture and Life Sciences North Carolina State University Raleigh NC 27695 USA

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Cecconi S., Ciccarelli C., Barberi M., Macchiarelli G., Canipari R. Granulosa Cell-Oocyte Interactions. Eur. J. Obstet. Gynecol. Reprod. Biol. 2004;115((Suppl 1)):S19–S22. doi: 10.1016/j.ejogrb.2004.01.010. PubMed DOI

Turathum B., Gao E.M., Chian R.C. The Function of Cumulus Cells in Oocyte Growth and Maturation and in Subsequent Ovulation and Fertilization. Cells. 2021;10:2292. doi: 10.3390/cells10092292. PubMed DOI PMC

Kidder G.M., Mhawi A.A. Gap Junctions and Ovarian Folliculogenesis. Reproduction. 2002;123:613–620. doi: 10.1530/rep.0.1230613. PubMed DOI

Strączyńska P., Papis K., Morawiec E., Czerwiński M., Gajewski Z., Olejek A., Bednarska-Czerwińska A. Signaling Mechanisms and Their Regulation during in Vivo or in Vitro Maturation of Mammalian Oocytes. Reprod. Biol. Endocrinol. 2022;20:37. doi: 10.1186/s12958-022-00906-5. PubMed DOI PMC

Robker R.L., Richards J.S. Hormone-Induced Proliferation and Differentiation of Granulosa Cells: A Coordinated Balance of the Cell Cycle Regulators Cyclin D2 and P27Kip1. Mol. Endocrinol. 1998;12:924–940. doi: 10.1210/mend.12.7.0138. PubMed DOI

Wang J., Chu K., Wang Y., Li J., Fu J., Zeng Y.A., Li W. Procr-Expressing Granulosa Cells Are Highly Proliferative and Are Important for Follicle Development. iScience. 2021;24:102065. doi: 10.1016/j.isci.2021.102065. PubMed DOI PMC

Pan B., Liu C., Zhan X., Li J. Protegrin-1 Regulates Porcine Granulosa Cell Proliferation via the EGFR-ERK1/2/P38 Signaling Pathway in Vitro. Front. Physiol. 2021;12:733. doi: 10.3389/fphys.2021.673777. PubMed DOI PMC

Kranc W., Brązert M., Budna J., Celichowski P., Bryja A., Nawrocki M.J., Ożegowska K., Jankowski M., Chermuła B., Dyszkiewicz-Konwińska M., et al. Genes Responsible for Proliferation, Differentiation, and Junction Adhesion Are Significantly up-Regulated in Human Ovarian Granulosa Cells during a Long-Term Primary in Vitro Culture. Histochem. Cell Biol. 2019;151:125–143. doi: 10.1007/s00418-018-1750-1. PubMed DOI PMC

Kulus J., Kulus M., Kranc W., Jopek K., Zdun M., Józkowiak M., Jáskowski J.M., Piotrowska-Kempisty H., Bukowska D., Antosik P., et al. Transcriptomic Profile of New Gene Markers Encoding Proteins Responsible for Structure of Porcine Ovarian Granulosa Cells. Biology. 2021;10:1214. doi: 10.3390/biology10111214. PubMed DOI PMC

Bader G.D., Hogue C.W.V. An Automated Method for Finding Molecular Complexes in Large Protein Interaction Networks. BMC Bioinform. 2003;4:2. doi: 10.1186/1471-2105-4-2. PubMed DOI PMC

Jiang X., Qin Y., Kun L., Zhou Y. The Significant Role of the Microfilament System in Tumors. Front. Oncol. 2021;11:333. doi: 10.3389/fonc.2021.620390. PubMed DOI PMC

McBeath R., Pirone D.M., Nelson C.M., Bhadriraju K., Chen C.S. Cell Shape, Cytoskeletal Tension, and RhoA Regulate Stem Cell Lineage Commitment. Dev. Cell. 2004;6:483–495. doi: 10.1016/S1534-5807(04)00075-9. PubMed DOI

Mathieu M., Martin-Jaular L., Lavieu G., Théry C. Specificities of Secretion and Uptake of Exosomes and Other Extracellular Vesicles for Cell-to-Cell Communication. Nat. Cell Biol. 2019;21:9–17. doi: 10.1038/s41556-018-0250-9. PubMed DOI

Shen Y., You Y., Zhu K., Fang C., Chang D., Yu X. Exosomes in the f Ield of Reproduction: A Scientometric Study and Visualization Analysis. Front. Pharmacol. 2022;13:1001652. doi: 10.3389/fphar.2022.1001652. PubMed DOI PMC

Muñoz E.L., Fuentes F.B., Felmer R.N., Yeste M., Arias M.E. Extracellular Vesicles in Mammalian Reproduction: A Review. Zygote. 2022;30:440–463. doi: 10.1017/S0967199422000090. PubMed DOI

de ávila A.C.F.C.M., Andrade G.M., Bridi A., Gimenes L.U., Meirelles F.V., Perecin F., da Silveira J.C. Extracellular Vesicles and Its Advances in Female Reproduction. Anim. Reprod. 2020;16:31–38. doi: 10.21451/1984-3143-AR2018-0101. PubMed DOI PMC

Llobat L. Extracellular Vesicles and Domestic Animal Reproduction. Res. Vet. Sci. 2021;136:166–173. doi: 10.1016/j.rvsc.2021.02.016. PubMed DOI

Lan Y., Jin Q., Xie H., Yan C., Ye Y., Zhao X., Chen Z., Xie Z. Exosomes Enhance Adhesion and Osteogenic Differentiation of Initial Bone Marrow Stem Cells on Titanium Surfaces. Front. Cell Dev. Biol. 2020;8:1216. doi: 10.3389/fcell.2020.583234. PubMed DOI PMC

Sung B.H., Parent C.A., Weaver A.M. Extracellular Vesicles: Critical Players during Cell Migration. Dev. Cell. 2021;56:1861–1874. doi: 10.1016/j.devcel.2021.03.020. PubMed DOI PMC

Miller C.M., Enninga E.A.L., Rizzo S.A., Phillipps J., Guerrero-Cazares H., Destephano C.C., Peterson T.E., Stalboerger P.G., Behfar A., Khan Z. Platelet-Derived Exosomes Induce Cell Proliferation and Wound Healing in Human Endometrial Cells. Regen. Med. 2022;17:805–817. doi: 10.2217/rme-2022-0095. PubMed DOI

Jiang H., Zhao H., Zhang M., He Y., Li X., Xu Y., Liu X. Hypoxia Induced Changes of Exosome Cargo and Subsequent Biological Effects. Front. Immunol. 2022;13:1140. doi: 10.3389/fimmu.2022.824188. PubMed DOI PMC

Karampoga A., Tzaferi K., Koutsakis C., Kyriakopoulou K., Karamanos N.K. Exosomes and the Extracellular Matrix: A Dynamic Interplay in Cancer Progression. Int. J. Dev. Biol. 2022;66:97–102. doi: 10.1387/ijdb.210120nk. PubMed DOI

Walma D.A.C., Yamada K.M. The Extracellular Matrix in Development. Development. 2020;147:175596. doi: 10.1242/dev.175596. PubMed DOI PMC

Mecham R.P. Overview of Extracellular Matrix. Curr. Protoc. Cell Biol. 2012;57:10.1.1–10.1.16. doi: 10.1002/0471143030.cb1001s57. PubMed DOI

Jones M.C., Zha J., Humphries M.J. Connections between the Cell Cycle, Cell Adhesion and the Cytoskeleton. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2019;374:20180227. doi: 10.1098/rstb.2018.0227. PubMed DOI PMC

Forth S., Kapoor T.M. The Mechanics of Microtubule Networks in Cell Division. J. Cell Biol. 2017;216:1525–1531. doi: 10.1083/jcb.201612064. PubMed DOI PMC

Sanghvi-Shah R., Weber G.F. Intermediate Filaments at the Junction of Mechanotransduction, Migration, and Development. Front. Cell Dev. Biol. 2017;5:81. doi: 10.3389/fcell.2017.00081. PubMed DOI PMC

Kamranvar S.A., Rani B., Johansson S. Cell Cycle Regulation by Integrin-Mediated Adhesion. Cells. 2022;11:2521. doi: 10.3390/cells11162521. PubMed DOI PMC

Baruah J., Wary K.K. Exosomes in the Regulation of Vascular Endothelial Cell Regeneration. Front. Cell Dev. Biol. 2020;7:353. doi: 10.3389/fcell.2019.00353. PubMed DOI PMC

Moncrieff L., Mozdziak P., Jeseta M., Machatkova M., Kranc W., Kempisty B. Ovarian Follicular Cells—Living in the Shadow of Stemness Cellular Competence. Med. J. Cell Biol. 2019;7:134–140. doi: 10.2478/acb-2019-0018. DOI

Stefańska K., Sibiak R., Hutchings G., Dompe C., Moncrieff L., Janowicz K., Jeseta M., Kempisty B., Machatkova M., Mozdziak P. Evidence for Existence of Molecular Stemness Markers in Porcine Ovarian Follicular Granulosa Cells. Med. J. Cell Biol. 2019;7:183–188. doi: 10.2478/acb-2019-0025. DOI

Hade M.D., Suire C.N., Suo Z. Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine. Cells. 2021;10:1959. doi: 10.3390/cells10081959. PubMed DOI PMC

Sergé A. The Molecular Architecture of Cell Adhesion: Dynamic Remodeling Revealed by Videonanoscopy. Front. Cell Dev. Biol. 2016;4:36. doi: 10.3389/fcell.2016.00036. PubMed DOI PMC

Martínez-Moro Á., González-Brusi L., Lamas-Toranzo I., O’callaghan E., Esteve-Codina A., Lonergan P., Bermejo-Álvarez P. RNA-Sequencing Reveals Genes Linked with Oocyte Developmental Potential in Bovine Cumulus Cells. Mol. Reprod. Dev. 2022;89:399–412. doi: 10.1002/mrd.23631. PubMed DOI PMC

Dinh D.T., Breen J., Akison L.K., DeMayo F.J., Brown H.M., Robker R.L., Russell D.L. Tissue-Specific Progesterone Receptor-Chromatin Binding and the Regulation of Progesterone-Dependent Gene Expression. Sci. Rep. 2019;9:11966. doi: 10.1038/s41598-019-48333-8. PubMed DOI PMC

Gurung S., Perocheau D., Touramanidou L., Baruteau J. The Exosome Journey: From Biogenesis to Uptake and Intracellular Signalling. Cell Commun. Signal. 2021;19:47. doi: 10.1186/s12964-021-00730-1. PubMed DOI PMC

Lenzini S., Bargi R., Chung G., Shin J.W. Matrix Mechanics and Water Permeation Regulate Extracellular Vesicle Transport. Nat. Nanotechnol. 2020;15:217–223. doi: 10.1038/s41565-020-0636-2. PubMed DOI PMC

Prada I., Meldolesi J. Binding and Fusion of Extracellular Vesicles to the Plasma Membrane of Their Cell Targets. Int. J. Mol. Sci. 2016;17:1296. doi: 10.3390/ijms17081296. PubMed DOI PMC

Mulcahy L.A., Pink R.C., Carter D.R.F. Routes and Mechanisms of Extracellular Vesicle Uptake. J. Extracell. Vesicles. 2014;3:1–14. doi: 10.3402/jev.v3.24641. PubMed DOI PMC

Guan S., Li Q., Liu P., Xuan X., Du Y. Experimental Immunology Umbilical Cord Blood-Derived Dendritic Cells Loaded with BGC823 Tumor Antigens and DC-Derived Exosomes Stimulate Efficient Cytotoxic T-Lymphocyte Responses and Antitumor Immunity in Vitro and in Vivo. Cent. Eur. J. Immunol. 2014;39:142–151. doi: 10.5114/ceji.2014.43713. PubMed DOI PMC

Kiss A.L., Botos E. Endocytosis via Caveolae: Alternative Pathway with Distinct Cellular Compartments to Avoid Lysosomal Degradation? J. Cell. Mol. Med. 2009;13:1228–1237. doi: 10.1111/j.1582-4934.2009.00754.x. PubMed DOI PMC

Svensson K.J., Christianson H.C., Wittrup A., Bourseau-Guilmain E., Lindqvist E., Svensson L.M., Mörgelin M., Belting M. Exosome Uptake Depends on ERK1/2-Heat Shock Protein 27 Signaling and Lipid Raft-Mediated Endocytosis Negatively Regulated by Caveolin-1. J. Biol. Chem. 2013;288:17713. doi: 10.1074/jbc.M112.445403. PubMed DOI PMC

Patel N.J., Ashraf A., Chung E.J. Extracellular Vesicles as Regulators of the Extracellular Matrix. Bioengineering. 2023;10:136. doi: 10.3390/bioengineering10020136. PubMed DOI PMC

Brigstock D.R. Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics. Cells. 2021;10:1596. doi: 10.3390/cells10071596. PubMed DOI PMC

Albacete-Albacete L., Navarro-Lérida I., López J.A., Martín-Padura I., Astudillo A.M., Ferrarini A., Van-Der-Heyden M., Balsinde J., Orend G., Vázquez J., et al. ECM Deposition Is Driven by Caveolin-1–Dependent Regulation of Exosomal Biogenesis and Cargo Sorting. J. Cell Biol. 2020;219:e202006178. doi: 10.1083/jcb.202006178. PubMed DOI PMC

Zhang Y., Liu Y., Liu H., Tang W.H. Exosomes: Biogenesis, Biologic Function and Clinical Potential. Cell Biosci. 2019;9:19. doi: 10.1186/s13578-019-0282-2. PubMed DOI PMC

Walker M.G., Volkmuth W. Cell Adhesion and Matrix Remodeling Genes Identified by Co-Expression Analysis. Gene Funct. Dis. 2002;3:109–112. doi: 10.1002/gnfd.200290000. DOI

Peng S., Zhu X., Zhao M., Zhang Y., Wang A., Chen M., Ye Z. Identification of Matrix-Remodeling Associated 5 as a Possible Molecular Oncotarget of Pancreatic Cancer. Cell Death Dis. 2023;14:157. doi: 10.1038/s41419-023-05684-5. PubMed DOI PMC

Laczko R., Csiszar K. Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways. Biomolecules. 2020;10:1093. doi: 10.3390/biom10081093. PubMed DOI PMC

Oleggini R., Biology A.D.D.-B. Lysyl Oxidase Regulates MMTV Promoter: Indirect Evidence of Histone H1 Involvement. Biochem. Cell Biol. 2011;89:522–532. doi: 10.1139/o11-049. PubMed DOI

Iturbide A., de Herreros A.G., Peiró S. A New Role for LOX and LOXL 2 Proteins in Transcription Regulation. Wiley Online Libr. 2015;282:1768–1773. doi: 10.1111/febs.12961. PubMed DOI

Gao A.E., Sullivan K.E., Black L.D. Lysyl Oxidase Expression in Cardiac Fibroblasts Is Regulated by A2β1 Integrin Interactions with the Cellular Microenvironment. Biochem. Biophys. Res. Commun. 2016;475:70–75. doi: 10.1016/j.bbrc.2016.05.037. PubMed DOI

Alcudia J.F., Martinez-Gonzalez J., Guadall A., Gonzalez-Diez M., Badimon L., Rodriguez C. Lysyl Oxidase and Endothelial Dysfunction: Mechanisms of Lysyl Oxidase down-Regulation by pro-Inflammatory Cytokines. Front. Biosci. 2008;13:2721–2727. doi: 10.2741/2879. PubMed DOI

Harlow C.R., Rae M., Davidson L., Trackman P.C., Hillier S.G. Lysyl Oxidase Gene Expression and Enzyme Activity in the Rat Ovary: Regulation by Follicle-Stimulating Hormone, Androgen, and Transforming Growth Factor-β Superfamily Members in Vitro. Endocrinology. 2003;144:154–162. doi: 10.1210/en.2002-220652. PubMed DOI

Zhang C., Ma J., Wang W., Sun Y., Sun K. Lysyl Oxidase Blockade Ameliorates Anovulation in Polycystic Ovary Syndrome. Hum. Reprod. 2018;33:2096–2106. doi: 10.1093/humrep/dey292. PubMed DOI

Yu J.E., Han S.Y., Wolfson B., Zhou Q. The Role of Endothelial Lipase in Lipid Metabolism, Inflammation, and Cancer. Histol. Histopathol. 2018;33:1–10. doi: 10.14670/HH-11-905. PubMed DOI PMC

Miller W.L., Bose H.S. Early Steps in Steroidogenesis: Intracellular Cholesterol Trafficking: Thematic Review Series: Genetics of Human Lipid Diseases. J. Lipid Res. 2011;52:2111. doi: 10.1194/jlr.R016675. PubMed DOI PMC

Bassi G., Sidhu S.K., Mishra S. The Expanding Role of Mitochondria, Autophagy and Lipophagy in Steroidogenesis. Cells. 2021;10:1851. doi: 10.3390/cells10081851. PubMed DOI PMC

Wang W., Zhu N., Yan T., Shi Y.N., Chen J., Zhang C.J., Xie X.J., Liao D.F., Qin L. The Crosstalk: Exosomes and Lipid Metabolism. Cell Commun. Signal. 2020;18:119. doi: 10.1186/s12964-020-00581-2. PubMed DOI PMC

Mikłosz A., Łukaszuk B., Chabowski A., Górski J. Treadmill Running Changes Endothelial Lipase Expression: Insights from Gene and Protein Analysis in Various Striated Muscle Tissues and Serum. Biomolecules. 2021;11:906. doi: 10.3390/biom11060906. PubMed DOI PMC

Wang C., Niimi M., Kitajima S., Matsuhisa F., Yan H., Dong S., Liang J., Fan J. Sex Hormones Affect Endothelial Lipase-Mediated Lipid Metabolism and Atherosclerosis. Lipids Health Dis. 2019;18:226. doi: 10.1186/s12944-019-1175-4. PubMed DOI PMC

Mourikes V.E., Santacruz Márquez R., Deviney A., Neff A.M., Laws M.J., Flaws J.A. Imidacloprid and Its Bioactive Metabolite, Desnitro-Imidacloprid, Differentially Affect Ovarian Antral Follicle Growth, Morphology, and Hormone Synthesis In Vitro. Toxics. 2023;11:349. doi: 10.3390/toxics11040349. PubMed DOI PMC

Samardzija Nenadov D., Pogrmic-Majkic K., Fa S., Stanic B., Tubic A., Andric N. Environmental Mixture with Estrogenic Activity Increases Hsd3b1 Expression through Estrogen Receptors in Immature Rat Granulosa Cells. J. Appl. Toxicol. 2018;38:879–887. doi: 10.1002/jat.3596. PubMed DOI

Munich S., Sobo-Vujanovic A., Buchser W.J., Beer-Stolz D., Vujanovic N.L. Dendritic Cell Exosomes Directly Kill Tumor Cells and Activate Natural Killer Cells via TNF Superfamily Ligands. Oncoimmunology. 2012;1:1074–1083. doi: 10.4161/onci.20897. PubMed DOI PMC

Yi X., Wu P., Fan Y., Gong Y., Liu J., Xiong J., Xu X. Identification of Candidate Genes Simultaneously Shared by Adipogenesis and Osteoblastogenesis from Human Mesenchymal Stem Cells. Folia Histochem. Cytobiol. 2022;60:179–190. doi: 10.5603/FHC.a2022.0012. PubMed DOI

Lei Y., Henderson B.R., Emmanuel C., Harnett P.R., Defazio A. Inhibition of ANKRD1 Sensitizes Human Ovarian Cancer Cells to Endoplasmic Reticulum Stress-Induced Apoptosis. Oncogene. 2015;34:485–495. doi: 10.1038/onc.2013.566. PubMed DOI

Elsafadi M., Manikandan M., Dawud R.A., Alajez N.M., Hamam R., Alfayez M., Kassem M., Aldahmash A., Mahmood A. Transgelin Is a TGFβ-Inducible Gene That Regulates Osteoblastic and Adipogenic Differentiation of Human Skeletal Stem Cells through Actin Cytoskeleston Organization. Cell Death Dis. 2016;7:e2321. doi: 10.1038/cddis.2016.196. PubMed DOI PMC

Lim M., Thompson J.G., Dunning K.R. HYPOXIA AND REPRODUCTIVE HEALTH: Hypoxia and Ovarian Function: Follicle Development, Ovulation, Oocyte Maturation. Reproduction. 2021;161:F33–F40. doi: 10.1530/REP-20-0509. PubMed DOI

Baddela V.S., Sharma A., Michaelis M., Vanselow J. HIF1 Driven Transcriptional Activity Regulates Steroidogenesis and Proliferation of Bovine Granulosa Cells. Sci. Rep. 2020;10:3906. doi: 10.1038/s41598-020-60935-1. PubMed DOI PMC

He G., Peng X., Wei S., Yang S., Li X., Huang M., Tang S., Jin H., Liu J., Zhang S., et al. Exosomes in the Hypoxic TME: From Release, Uptake and Biofunctions to Clinical Applications. Mol. Cancer. 2022;21:19. doi: 10.1186/s12943-021-01440-5. PubMed DOI PMC

Li L., Mu J., Zhang Y., Zhang C., Ma T., Chen L., Huang T., Wu J., Cao J., Feng S., et al. Stimulation by Exosomes from Hypoxia Preconditioned Human Umbilical Vein Endothelial Cells Facilitates Mesenchymal Stem Cells Angiogenic Function for Spinal Cord Repair. ACS Nano. 2022;16:10811–10823. doi: 10.1021/acsnano.2c02898. PubMed DOI

Nishimura R., Okuda K. Multiple Roles of Hypoxia in Ovarian Function: Roles of Hypoxia-Inducible Factor-Related and-Unrelated Signals during the Luteal Phase. Reprod. Fertil. Dev. 2015;28:1479–1486. doi: 10.1071/RD15010. PubMed DOI

Dompe C., Kulus M., Stefańska K., Kranc W., Chermuła B., Bryl R., Pieńkowski W., Nawrocki M.J., Petitte J.N., Stelmach B., et al. Human Granulosa Cells—Stemness Properties, Molecular Cross-Talk and Follicular Angiogenesis. Cells. 2021;10:1396. doi: 10.3390/cells10061396. PubMed DOI PMC

Xu X., Mu L., Li L., Liang J., Zhang S., Jia L., Yang X., Dai Y., Zhang J., Wang Y., et al. Imaging and Tracing the Pattern of Adult Ovarian Angiogenesis Implies a Strategy against Female Reproductive Aging. Sci. Adv. 2022;8:8683. doi: 10.1126/sciadv.abi8683. PubMed DOI PMC

Olejarz W., Kubiak-Tomaszewska G., Chrzanowska A., Lorenc T. Exosomes in Angiogenesis and Anti-Angiogenic Therapy in Cancers. Int. J. Mol. Sci. 2020;21:5840. doi: 10.3390/ijms21165840. PubMed DOI PMC

Chen S., Chen X., Luo Q., Liu X., Wang X., Cui Z., He A., He S., Jiang Z., Wu N., et al. Retinoblastoma Cell-Derived Exosomes Promote Angiogenesis of Human Vesicle Endothelial Cells through MicroRNA-92a-3p. Cell Death Dis. 2021;12:695. doi: 10.1038/s41419-021-03986-0. PubMed DOI PMC

Hettich B.F., Ben-Yehuda Greenwald M., Werner S., Leroux J.C. Exosomes for Wound Healing: Purification Optimization and Identification of Bioactive Components. Adv. Sci. 2020;7:2002596. doi: 10.1002/advs.202002596. PubMed DOI PMC

Zhou C., Zhang B., Yang Y., Jiang Q., Li T., Gong J., Tang H., Zhang Q. Stem Cell-Derived Exosomes: Emerging Therapeutic Opportunities for Wound Healing. Stem Cell Res. Ther. 2023;14:107. doi: 10.1186/s13287-023-03345-0. PubMed DOI PMC

Bo Y., Yang L., Liu B., Tian G., Li C., Zhang L., Yan Y. Exosomes from Human Induced Pluripotent Stem Cells-Derived Keratinocytes Accelerate Burn Wound Healing through MiR-762 Mediated Promotion of Keratinocytes and Endothelial Cells Migration. J. Nanobiotechnol. 2022;20:291. doi: 10.1186/s12951-022-01504-8. PubMed DOI PMC

Li D., Wu N. Mechanism and Application of Exosomes in the Wound Healing Process in Diabetes Mellitus. Diabetes Res. Clin. Pract. 2022;187:109882. doi: 10.1016/j.diabres.2022.109882. PubMed DOI

Samaras S.E., Almodóvar-García K., Wu N., Yu F., Davidson J.M. Global Deletion of Ankrd1 Results in a Wound-Healing Phenotype Associated with Dermal Fibroblast Dysfunction. Am. J. Pathol. 2015;185:96. doi: 10.1016/j.ajpath.2014.09.018. PubMed DOI PMC

Cai L., Xiong X., Kong X., Xie J. The Role of the Lysyl Oxidases in Tissue Repair and Remodeling: A Concise Review. Tissue Eng. Regen. Med. 2017;14:15. doi: 10.1007/s13770-016-0007-0. PubMed DOI PMC

Yung Y., Ophir L., Yerushalmi G.M., Baum M., Hourvitz A., Maman E. HAS2-AS1 Is a Novel LH/HCG Target Gene Regulating HAS2 Expression and Enhancing Cumulus Cells Migration. J. Ovarian Res. 2019;12:21. doi: 10.1186/s13048-019-0495-3. PubMed DOI PMC

Tan J.X., Wang X.Y., Li H.Y., Su X.L., Wang L., Ran L., Zheng K., Ren G.S. HYAL1 Overexpression Is Correlated with the Malignant Behavior of Human Breast Cancer. Int. J. Cancer. 2011;128:1303–1315. doi: 10.1002/ijc.25460. PubMed DOI

Deng H., Wang J., An R. Hyaluronic Acid-Based Hydrogels: As an Exosome Delivery System in Bone Regeneration. Front. Pharmacol. 2023;14:1131001. doi: 10.3389/fphar.2023.1131001. PubMed DOI PMC

Kimura N., Totsukawa K., Sato E. Significance of Mammalian Cumulus-Oocyte Complex Matrix in Oocyte Meiotic Maturation: Review of the Synthetic Control and Possible Roles of Hyaluronan (HA) and HA-Binding Protein. J. Mamm. Ova Res. 2006;23:36–51. doi: 10.1274/jmor.23.36. DOI

Ahn J., Han K.S., Heo J.H., Bang D., Kang Y.H., Jin H.A., Hong S.J., Lee J.H., Ham W.S. FOXC2 and CLIP4: A Potential Biomarker for Synchronous Metastasis of ≤7-Cm Clear Cell Renal Cell Carcinomas. Oncotarget. 2016;7:51423. doi: 10.18632/oncotarget.9842. PubMed DOI PMC

Liu Y., Su C.Y., Yan Y.Y., Wang J., Li J.J., Fu J.J., Wang Y.Q., Zhang J.Y. Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to Let-7c-5p and MiR-181b-5p. Front. Endocrinol. 2022;13:1395. doi: 10.3389/fendo.2022.926769. PubMed DOI PMC

Ma S., Song L., Bai Y., Wang S., Wang J., Zhang H., Wang F., He Y., Tian C., Qin G. Improved Intracellular Delivery of Exosomes by Surface Modification with Fluorinated Peptide Dendrimers for Promoting Angiogenesis and Migration of HUVECs. RSC Adv. 2023;13:11269–11277. doi: 10.1039/D3RA00300K. PubMed DOI PMC

Sung B.H., Ketova T., Hoshino D., Zijlstra A., Weaver A.M. Directional Cell Movement through Tissues Is Controlled by Exosome Secretion. Nat. Commun. 2015;6:7164. doi: 10.1038/ncomms8164. PubMed DOI PMC

Jimenez L., Yu H., McKenzie A.J., Franklin J.L., Patton J.G., Liu Q., Weaver A.M. Quantitative Proteomic Analysis of Small and Large Extracellular Vesicles (EVs) Reveals Enrichment of Adhesion Proteins in Small EVs. J. Proteome Res. 2019;18:947–959. doi: 10.1021/acs.jproteome.8b00647. PubMed DOI PMC

Yuan X., Zhou X., Qiao X., Wu Q., Yao Z., Jiang Y., Zhang H., Zhang Z., Wang X., Li J. FoxA2 and P53 Regulate the Transcription of HSD17B1 in Ovarian Granulosa Cells of Pigs. Reprod. Domest. Anim. 2021;56:74–82. doi: 10.1111/rda.13850. PubMed DOI

Yu L., Liu M., Wang Z., Liu T., Liu S., Wang B., Pan B., Dong X., Guo W. Correlation between Steroid Levels in Follicular Fluid and Hormone Synthesis Related Substances in Its Exosomes and Embryo Quality in Patients with Polycystic Ovary Syndrome. Reprod. Biol. Endocrinol. 2021;19:74. doi: 10.1186/s12958-021-00749-6. PubMed DOI PMC

Karman B.N., Basavarajappa M.S., Hannon P., Flaws J.A. Dioxin Exposure Reduces the Steroidogenic Capacity of Mouse Antral Follicles Mainly at the Level of HSD17B1 without Altering Atresia. Toxicol. Appl. Pharmacol. 2012;264:1–12. doi: 10.1016/j.taap.2012.07.031. PubMed DOI PMC

Wang C., Zhao Y., Yuan Z.Y., Wu Y., Zhao Z., Wu C., Hou J., Zhang M. Genome-Wide Identification of MRNAs, LncRNAs, and Proteins, and Their Relationship with Sheep Fecundity. Front. Genet. 2022;12:2667. doi: 10.3389/fgene.2021.750947. PubMed DOI PMC

Zhou Q.Y., Wan M.C., Wei Q.P., Song Q.L., Xiong L.G., Huo J.H., Huang J.N. Expression, Regulation, and Functional Characterization of FST Gene in Porcine Granulosa Cells. Anim. Biotechnol. 2016;27:295–302. doi: 10.1080/10495398.2016.1184675. PubMed DOI

Patton B.K., Madadi S., Pangas S.A. Control of Ovarian Follicle Development by TGF-β Family Signaling. Curr. Opin. Endocr. Metab. Res. 2021;18:102–110. doi: 10.1016/j.coemr.2021.03.001. PubMed DOI PMC

Bai X., Wang S. Signaling Pathway Intervention in Premature Ovarian Failure. Front. Med. 2022;9:3545. doi: 10.3389/fmed.2022.999440. PubMed DOI PMC

Wang C., Sun Y. Induction of Collagen I by CXCL10 in Ovarian Theca–Stroma Cells via the JNK Pathway. Front. Endocrinol. 2022;13:823740. doi: 10.3389/fendo.2022.823740. PubMed DOI PMC

Budna J., Chachuła A., Kaźmierczak D., Rybska M., Ciesiółka S., Bryja A., Kranc W., Borys S., Zok A., Bukowska D., et al. Morphogenesis-Related Gene-Expression Profile in Porcine Oocytes before and after in Vitro Maturation. Zygote. 2017;25:331–340. doi: 10.1017/S096719941700020X. PubMed DOI

Stelcer E., Komarowska H., Jopek K., Żok A., Iżycki D., Malińska A., Szczepaniak B., Komekbai Z., Karczewski M., Wierzbicki T., et al. Biological Response of Adrenal Carcinoma and Melanoma Cells to Mitotane Treatment. Oncol. Lett. 2022;23:120. doi: 10.3892/ol.2022.13240. PubMed DOI PMC

Dennis G., Sherman B.T., Hosack D.A., Yang J., Gao W., Lane H.C., Lempicki R.A. DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003;4:P3. doi: 10.1186/gb-2003-4-5-p3. PubMed DOI

Extract and Visualize the Results of Multivariate Data Analyses [R Package Factoextra Version 1.0.7] | Semantic Scholar. [(accessed on 5 March 2023)]. Available online: https://www.semanticscholar.org/paper/Extract-and-Visualize-the-Results-of-Multivariate-Kassambara-Mundt/5cb503e3db8609405d9f286fadc2a8bb867e5b6e.

Golkar-Narenji A., Antosik P., Nolin S., Rucinski M., Jopek K., Zok A., Sobolewski J., Jankowski M., Zdun M., Bukowska D., et al. Gene Ontology Groups and Signaling Pathways Regulating the Process of Avian Satellite Cell Differentiation. Genes. 2022;13:242. doi: 10.3390/genes13020242. PubMed DOI PMC

Benjamini Y., Cohen R. Weighted False Discovery Rate Controlling Procedures for Clinical Trials. Biostatistics. 2017;18:91–104. doi: 10.1093/biostatistics/kxw030. PubMed DOI PMC

Gu Z., Eils R., Schlesner M. Complex Heatmaps Reveal Patterns and Correlations in Multidimensional Genomic Data. Bioinformatics. 2016;32:2847–2849. doi: 10.1093/bioinformatics/btw313. PubMed DOI

Yu G., Wang L.G., Han Y., He Q.Y. ClusterProfiler: An R Package for Comparing Biological Themes among Gene Clusters. Omics. 2012;16:284–287. doi: 10.1089/omi.2011.0118. PubMed DOI PMC