A review on artificial ovary fabrication using bioengineering and factors affecting the improvement of its outcomes

Document Type : Review article

Authors

1 Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

2 Department of Stem Cells Technology and Tissue Regeneration, University of Science and Culture, Tehran, Iran

3 Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

4 Department of Obstetrics and Gynecology, Arash Hospital, Tehran, Iran

5 Department of Obstetrics and Gynecology, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Efforts to preserve fertility and improve the quality of life for cancer survivors, patients with polycystic ovary syndrome (PCOS), premature ovarian failure (POF), individuals with autoimmune diseases (1), and those with genetic disorders such as Turner syndrome have gained increasing attention. Due to the gonadotoxic effects of cancer treatments, preserving fertility prior to remedy has become a clinical and ethical imperative in cancer care (2). Egg and embryo freezing are standard methods of fertility preservation and aren’t used to prevent premature ovarian failure, particularly in young girls. Additionally, there is a risk of malignant cell recurrence with ovarian tissue cryopreservation and transplantation. In this context, artificial ovary that mimics ovarian natural condition holds great importance. Ovarian tissue engineering provides a three-dimensional system to support follicular growth and oocyte meiosis resumption, and a new strategy for treating the ovarian failure (3). To realize the idea of artificial ovary, a suitable scaffold is necessary to support somatic cells and follicular complex for production of competence oocyte, and identification and use of factors can improve the performance of artificial ovaries and bring them closer to natural samples. Various studies have found the use of follicular fluid and cumulus cells conditioned medium to be useful in achieving this goal.

Keywords

Main Subjects

References

  1. Vanni V, De Lorenzo R, Privitera L, Canti V, Viganò P, Rovere-Querini P. Safety of fertility treatments in women with systemic autoimmune diseases (SADs). Expert Opinion on Drug Safety. 2019;18(9):841-52.
  2. Dolmans M-M, Amorim CA. Fertility preservation: construction and use of artificial ovaries. Reproduction. 2019;158(5):F15-F25.
  3. Dadashzadeh A, Moghassemi S, Shavandi A, Amorim CA. A review on biomaterials for ovarian tissue engineering. Acta biomaterialia. 2021;135:48-63.
  4. Ramírez-González JA, Vaamonde-Lemos R, Cunha-Filho JS, Varghese AC, Swanson RJ. Overview of the female reproductive system. Exercise and human reproduction: Springer; 2016. p. 19-46.
  5. Sittadjody S, Saul JM, McQuilling JP, Joo S, Register TC, Yoo JJ, et al. In vivo transplantation of 3D encapsulated ovarian constructs in rats corrects abnormalities of ovarian failure. Nature communications. 2017;8(1):1-13.
  6. Silvestris E, Minoia C, Guarini A, Opinto G, Negri A, Dellino M, et al. Ovarian Stem Cells (OSCs) from the Cryopreserved Ovarian Cortex: A Potential for Neo-Oogenesis in Women with Cancer-Treatment Related Infertility: A Case Report and a Review of Literature. Current Issues in Molecular Biology. 2022;44(5):2309-20.
  7. Chen J, Torres-de la Roche LA, Kahlert UD, Isachenko V, Huang H, Hennefründ J, et al. Artificial Ovary for Young Female Breast Cancer Patients. Frontiers in Medicine. 2022;9.
  8. Cho E, Kim YY, Noh K, Ku SY. A new possibility in fertility preservation: The artificial ovary. Journal of Tissue Engineering and Regenerative Medicine. 2019;13(8):1294-315.
  9. Amorim CA, Van Langendonckt A, David A, Dolmans M-M, Donnez J. Survival of human pre-antral follicles after cryopreservation of ovarian tissue, follicular isolation and in vitro culture in a calcium alginate matrix. Human Reproduction. 2009;24(1):92-9.
  10. Luyckx V, Dolmans M-M, Vanacker J, Scalercio SR, Donnez J, Amorim CA. First step in developing a 3D biodegradable fibrin scaffold for an artificial ovary. Journal of ovarian research. 2013;6(1):1-10.
  11. Luyckx V, Dolmans M-M, Vanacker J, Legat C, Moya CF, Donnez J, et al. A new step toward the artificial ovary: survival and proliferation of isolated murine follicles after autologous transplantation in a fibrin scaffold. Fertility and sterility. 2014;101(4):1149-56.
  12. Chiti MC, Dolmans M-M, Orellana R, Soares M, Paulini F, Donnez J, et al. Influence of follicle stage on artificial ovary outcome using fibrin as a matrix. Human Reproduction. 2016;31(2):427-35.
  13. Dath C, Dethy A, Van Langendonckt A, Van Eyck A-S, Amorim C, Luyckx V, et al. Endothelial cells are essential for ovarian stromal tissue restructuring after xenotransplantation of isolated ovarian stromal cells. Human reproduction. 2011;26(6):1431-9.
  14. Soares M, Sahrari K, Chiti MC, Amorim C, Ambroise J, Donnez J, et al. The best source of isolated stromal cells for the artificial ovary: medulla or cortex, cryopreserved or fresh? Human reproduction. 2015;30(7):1589-98.
  15. Chiti MC, Dolmans M-M, Lucci C, Paulini F, Donnez J, Amorim C. Further insights into the impact of mouse follicle stage on graft outcome in an artificial ovary environment. MHR: Basic science of reproductive medicine. 2017;23(6):381-92.
  16. Shahri PAK, Chiti MC, Amorim CA. Isolation and characterization of the human ovarian cell population for transplantation into an artificial ovary. Animal reproduction. 2019;16(1):39.
  17. Khaleghi S, Eivazkhani F, Moini A, Novin MG, Nazarian H, Fathi R. Isolation of Viable Ovarian Cells From Cryopreserved Ovarian Tissues of Women Undergoing Chemotherapy Induced Premature Ovarian Failure (Chemo-POF) and Their Qualification by Flow Cytometry.
  18. Telfer E, Anderson R. The existence and potential of germline stem cells in the adult mammalian ovary. Climacteric. 2019;22(1):22-6.
  19. Zhang A, Xu B, Sun Y, Lu X, Niu Z, Chen Q, et al. The effect of human cumulus cells on the maturation and developmental potential of immature oocytes in ICSI cycles. Journal of assisted reproduction and genetics. 2012;29(4):313-9.
  20. Madkour A, Bouamoud N, Kaarouch I, Louanjli N, Saadani B, Assou S, et al. Follicular fluid and supernatant from cultured cumulus-granulosa cells improve in vitro maturation in patients with polycystic ovarian syndrome. Fertility and sterility. 2018;110(4):710-9.
  21. Vithoulkas A, Levanduski M, Goudas VT, Illmensee K. Co-culture of human embryos with autologous cumulus cell clusters and its beneficial impact of secreted growth factors on preimplantation development as compared to standard embryo culture in assisted reproductive technologies (ART). Middle East Fertility Society Journal. 2017;22(4):317-22.
  22. Bhadarka HK, Patel NH, Patel NH, Patel M, Patel KB, Sodagar NR, et al. Impact of embryo co-culture with cumulus cells on pregnancy & implantation rate in patients undergoing in vitro fertilization using donor oocyte. The Indian Journal of Medical Research. 2017;146(3):341.
  23. Luddi A, Capaldo A, Focarelli R, Gori M, Morgante G, Piomboni P, et al. Antioxidants reduce oxidative stress in follicular fluid of aged women undergoing IVF. Reprod Biol Endocrinol. 2016;14(1):1-7.
  24. Dumesic DA, Meldrum DR, Katz-Jaffe MG, Krisher RL, Schoolcraft WB. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. Fertility and sterility. 2015;103(2):303-16.
  25. Mirzaeian L, Eftekhari-Yazdi P, Esfandiari F, Eivazkhani F, Rezazadeh Valojerdi M, Moini A, et al. Induction of Mouse Peritoneum Mesenchymal Stem Cells into Germ Cell-Like Cells Using Follicular Fluid and Cumulus Cells-Conditioned Media. Stem Cells Dev. 2019;28(8):554-64.
  26. Jarkovska K, Kupcova Skalnikova H, Halada P, Hrabakova R, Moos J, Rezabek K, et al. Development of ovarian hyperstimulation syndrome: interrogation of key proteins and biological processes in human follicular fluid of women undergoing in vitro fertilization. Mol Hum Reprod. 2011;17(11):679-92.
  27. Regiani T, Cordeiro FB, da Costa LdVT, Salgueiro J, Cardozo K, Carvalho VM, et al. Follicular fluid alterations in endometriosis: label-free proteomics by MSE as a functional tool for endometriosis. Syst Biol Reprod Med. 2015;61(5):263-76.
  28. Ambekar AS, Kelkar DS, Pinto SM, Sharma R, Hinduja I, Zaveri K, et al. Proteomics of follicular fluid from women with polycystic ovary syndrome suggests molecular defects in follicular development. The Journal of Clinical Endocrinology & Metabolism. 2015;100(2):744-53.
  29. Kim YS, Kim MS, Lee SH, Choi BC, Lim JM, Cha KY, et al. Proteomic analysis of recurrent spontaneous abortion: identification of an inadequately expressed set of proteins in human follicular fluid. Proteomics. 2006;6(11):3445-54.
  30. Skinner MK. Regulation of primordial follicle assembly and development. Hum Reprod Update. 2005;11(5):461-71.
  31. Andrei D, Nagy RA, van Montfoort A, Tietge U, Terpstra M, Kok K, et al. Differential miRNA Expression Profiles in Cumulus and Mural Granulosa Cells from Human Pre-ovulatory Follicles. Microrna. 2019;8(1):61-7.
  32. Atrabi MJ, Akbarinejad V, Khanbabaee R, Dalman A, Amorim CA, Najar-Asl M, et al. Formation and activation induction of primordial follicles using granulosa and cumulus cells conditioned media. J Cell Physiol. 2019;234(7):10148-56.
  33. Zhang J, Liu W, Sun X, Kong F, Zhu Y, Lei Y, et al. Inhibition of mTOR Signaling Pathway Delays Follicle Formation in Mice. J Cell Physiol. 2017;232(3):585-95.
  34. Chang HM, Qiao J, Leung PC. Oocyte-somatic cell interactions in the human ovary-novel role of bone morphogenetic proteins and growth differentiation factors. Hum Reprod Update. 2016;23(1):1-18.
  35. Makabe S, Naguro T, Stallone T. Oocyte-follicle cell interactions during ovarian follicle development, as seen by high resolution scanning and transmission electron microscopy in humans. Microsc Res Tech. 2006;69(6):436-49.
  36. Huang Z, Wells D. The human oocyte and cumulus cells relationship: new insights from the cumulus cell transcriptome. Mol Hum Reprod. 2010;16(10):715-25.
  37. Kwon H, Choi DH, Bae JH, Kim JH, Kim YS. mRNA expression pattern of insulin-like growth factor components of granulosa cells and cumulus cells in women with and without polycystic ovary syndrome according to oocyte maturity. Fertil Steril. 2010;94(6):2417-20.
  38. Zhao SY, Qiao J, Chen YJ, Liu P, Li J, Yan J. Expression of growth differentiation factor-9 and bone morphogenetic protein-15 in oocytes and cumulus granulosa cells of patients with polycystic ovary syndrome. Fertil Steril. 2010;94(1):261-7.
  39. Uhde K, van Tol HTA, Stout TAE, Roelen BAJ. Metabolomic profiles of bovine cumulus cells and cumulus-oocyte-complex-conditioned medium during maturation in vitro. Sci Rep. 2018;8(1):9477-.
  40. Sadat Tahajjodi S, Farashahi Yazd E, Agha-Rahimi A, Aflatoonian R, Ali Khalili M, Mohammadi M, et al. Biological and physiological characteristics of human cumulus cells in adherent culture condition. International journal of reproductive biomedicine. 2020;18(1):1-10.
  41. Zolfaghar M, Mirzaeian L, Beiki B, Naji T, Moini A, Eftekhari-Yazdi P, et al. Wharton's jelly derived mesenchymal stem cells differentiate into oocyte like cells in vitro by follicular fluid and cumulus cells conditioned medium. Heliyon. 2020;6(10):e04992.
  42. de Souza G, Costa J, da Cunha E, Passos J, Ribeiro R, Saraiva M, et al. Bovine ovarian stem cells differentiate into germ cells and oocyte‐like structures after culture in vitro. Reproduction in Domestic Animals. 2017;52(2):243-50.
  43. Shah SM, Saini N, Ashraf S, Singh MK, Manik RS, Singla SK, et al. Cumulus cell-conditioned medium supports embryonic stem cell differentiation to germ cell-like cells. Reproduction, fertility and development. 2017;29(4):679-93.
  44. Qiu P, Bai Y, Pan S, Li W, Liu W, Hua J. Gender depended potentiality of differentiation of human umbilical cord mesenchymal stem cells into oocyte‐Like cells in vitro. Cell Biochemistry and Function. 2013;31(5):365-73.
  45. Mirzaeian L, Eftekhari-Yazdi P, Esfandiari F, Eivazkhani F, Rezazadeh Valojerdi M, Moini A, et al. Induction of mouse peritoneum mesenchymal stem cells into germ cell-like cells using follicular fluid and cumulus cells-conditioned media. Stem Cells and Development. 2019;28(8):554-64.
  46. Molaeeghaleh N, Tork S, Abdi S, Movassaghi S. Evaluating the effects of different concentrations of human follicular fluid on growth, development, and PCNA gene expression of mouse ovarian follicles. Cells Tissues Organs. 2020;209(2–3):75-82.
  47. Nikolova MP, Chavali MS. Recent advances in biomaterials for 3D scaffolds: A review. Bioactive materials. 2019;4:271-92.
  48. Asti A, Gioglio L. Natural and synthetic biodegradable polymers: different scaffolds for cell expansion and tissue formation. The International journal of artificial organs. 2014;37(3):187-205.
  49. Wagner V, Dullaart A, Bock A-K, Zweck A. The emerging nanomedicine landscape. Nature biotechnology. 2006;24(10):1211-7.
  50. Srikanth M, Kessler JA. Nanotechnology—novel therapeutics for CNS Nature reviews neurology. 2012;8(6):307-18.
  51. Pascual-Gil S, Garbayo E, Díaz-Herráez P, Prosper F, Blanco-Prieto MJ. Heart regeneration after myocardial infarction using synthetic biomaterials. Journal of Controlled Release. 2015;203:23-38.
  52. Wu M, Guo Y, Wei S, Xue L, Tang W, Chen D, et al. Biomaterials and advanced technologies for the evaluation and treatment of ovarian aging. Journal of Nanobiotechnology. 2022;20(1):1-41.
  53. Frantz C, Stewart KM, Weaver VM. The extracellular matrix at a glance. Journal of cell science. 2010;123(24):4195-200.
  54. Clause KC, Barker TH. Extracellular matrix signaling in morphogenesis and repair. Current opinion in biotechnology. 2013;24(5):830-3.
  55. Claudio-Rizo JA, Rangel-Argote M, Castellano LE, Delgado J, Mata-Mata JL, Mendoza-Novelo B. Influence of residual composition on the structure and properties of extracellular matrix derived hydrogels. Materials Science and Engineering: C. 2017;79:793-801.
  56. Yang J, Dang H, Xu Y. Recent advancement of decellularization extracellular matrix for tissue engineering and biomedical application. Artificial Organs. 2022;46(4):549-67.
  57. Hynes RO, Naba A. Overview of the matrisome—an inventory of extracellular matrix constituents and functions. Cold Spring Harbor perspectives in biology. 2012;4(1):a004903.
  58. Rodgers RJ, Irving-Rodgers HF, Russell DL. Extracellular matrix of the developing ovarian follicle. REPRODUCTION-CAMBRIDGE-. 2003;126(4):415-24.
  59. Sawkins MJ, Saldin LT, Badylak SF, White LJ. ECM hydrogels for regenerative medicine. Extracellular Matrix for Tissue Engineering and Biomaterials: Springer; 2018. p. 27-58.
  60. Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Advanced drug delivery reviews. 2016;97:4-27.
  61. Francés-Herrero E, Rodríguez-Eguren A, Gómez-Álvarez M, de Miguel-Gómez L, Ferrero H, Cervelló I. Future Challenges and Opportunities of Extracellular Matrix Hydrogels in Female Reproductive Medicine. International journal of molecular sciences. 2022;23(7):3765.
  62. Lu H, Ju D-d, Yang G-d, Zhu L-y, Yang X-m, Li J, et al. Targeting cancer stem cell signature gene SMOC-2 Overcomes chemoresistance and inhibits cell proliferation of endometrial carcinoma. EBioMedicine. 2019;40:276-89.
  63. Poornejad N, Frost TS, Scott DR, Elton BB, Reynolds PR, Roeder BL, et al. Freezing/thawing without cryoprotectant damages native but not decellularized porcine renal tissue. Organogenesis. 2015;11(1):30-45.
  64. Hassanpour A, Talaei-Khozani T, Kargar-Abarghouei E, Razban V, Vojdani Z. Decellularized human ovarian scaffold based on a sodium lauryl ester sulfate (SLES)-treated protocol, as a natural three-dimensional scaffold for construction of bioengineered ovaries. Stem cell research & therapy. 2018;9(1):1-13.
  65. Laronda MM, Jakus AE, Whelan KA, Wertheim JA, Shah RN, Woodruff TK. Initiation of puberty in mice following decellularized ovary transplant. Biomaterials. 2015;50:20-9.
  66. Pennarossa G, De Iorio T, Gandolfi F, Brevini TA. Ovarian decellularized bioscaffolds provide an optimal microenvironment for cell growth and differentiation in vitro. Cells. 2021;10(8):2126.
  67. Zheng J, Liu Y, Hou C, Li Z, Yang S, Liang X, et al. Ovary-derived Decellularized Extracellular Matrix-based Bioink for Fabricating 3D Primary Ovarian Cells-laden Structures for Mouse Ovarian Failure Correction. International Journal of Bioprinting. 2022;8(3).
  68. Alshaikh AB, Padma AM, Dehlin M, Akouri R, Song MJ, Brännström M, et al. Decellularization and recellularization of the ovary for bioengineering applications; studies in the mouse. Reproductive Biology and Endocrinology. 2020;18(1):1-10.
  69. Alshaikh AB, Padma AM, Dehlin M, Akouri R, Song MJ, Brännström M, et al. Decellularization of the mouse ovary: comparison of different scaffold generation protocols for future ovarian bioengineering. Journal of ovarian research. 2019;12(1):1-9.
  70. Liu W-Y, Lin S-G, Zhuo R-Y, Xie Y-Y, Pan W, Lin X-F, et al. Xenogeneic decellularized scaffold: a novel platform for ovary regeneration. Tissue Engineering Part C: Methods. 2017;23(2):61-71.
  71. Sistani MN, Zavareh S, Valujerdi MR, Salehnia M. Characteristics of a decellularized human ovarian tissue created by combined protocols and its interaction with human endometrial mesenchymal cells. Progress in Biomaterials. 2021;10(3):195-206.
  72. Pors S, Ramløse M, Nikiforov D, Lundsgaard K, Cheng J, Andersen CY, et al. Initial steps in reconstruction of the human ovary: survival of pre-antral stage follicles in a decellularized human ovarian scaffold. Human Reproduction. 2019;34(8):1523-35.
  73. Kawecki M, Łabuś W, Klama‐Baryla A, Kitala D, Kraut M, Glik J, et al. A review of decellurization methods caused by an urgent need for quality control of cell‐free extracellular matrix'scaffolds and their role in regenerative medicine. Journal of Biomedical Materials Research Part B: Applied Biomaterials. 2018;106(2):909-23.
  74. Gilpin A, Yang Y. Decellularization strategies for regenerative medicine: from processing techniques to applications. BioMed research international. 2017;2017.
  75. Badylak SF. Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: factors that influence the host response. Annals of biomedical engineering. 2014;42(7):1517-27.
  76. Eivazkhani F, Abtahi NS, Tavana S, Mirzaeian L, Abedi F, Ebrahimi B, et al. Evaluating two ovarian decellularization methods in three species. Materials Science and Engineering: C. 2019;102:670-82.
  77. Pennarossa G, Ghiringhelli M, Gandolfi F, Brevini TA. Whole-ovary decellularization generates an effective 3D bioscaffold for ovarian bioengineering. Journal of assisted reproduction and genetics. 2020;37(6):1329-39.
  78. Nikniaz H, Zandieh Z, Nouri M, Daei-Farshbaf N, Aflatoonian R, Gholipourmalekabadi M, et al. Comparing various protocols of human and bovine ovarian tissue decellularization to prepare extracellular matrix-alginate scaffold for better follicle development in vitro. BMC biotechnology. 2021;21:1-8.
  79. Alaee S, Asadollahpour R, Hosseinzadeh Colagar A, Talaei-Khozani T. The decellularized ovary as a potential scaffold for maturation of preantral ovarian follicles of prepubertal mice. Systems Biology in Reproductive Medicine. 2021;67(6):413-27.
  80. Pennarossa G, Ghiringhelli M, Gandolfi F, Brevini TA. Creation of a bioengineered ovary: isolation of female germline stem cells for the repopulation of a decellularized ovarian bioscaffold. Next Generation Culture Platforms for Reliable In Vitro Models: Springer; 2021. p. 139-49.
  81. Almeida GHDR, da Silva-Júnior LN, Gibin MS, Dos Santos H, de Oliveira Horvath-Pereira B, Pinho LBM, et al. Perfusion and ultrasonication produce a decellularized porcine whole-ovary scaffold with a preserved microarchitecture. Cells. 2023;12(14):1864.
  82. Kinnear HM, Tomaszewski CE, Chang FL, Moravek MB, Xu M, Padmanabhan V, et al. The ovarian stroma as a new frontier. Reproduction. 2020;160(3):R25-R39.
  83. Mescher A. Epithelial tissue. New York, NY: McGraw-Hill Education; 2018.
  84. Knight PG, Glister C. TGF-β superfamily members and ovarian follicle development. Reproduction. 2006;132(2):191-206.
  85. Wang S, Zheng Y, Li J, Yu Y, Zhang W, Song M, et al. Single-cell transcriptomic atlas of primate ovarian aging. Cell. 2020;180(3):585-600. e19.
  86. O’Neill KE, Maher JY, Laronda MM, Duncan FE, LeDuc RD, Lujan ME, et al. Anatomic nomenclature and 3-dimensional regional model of the human ovary: call for a new paradigm. American journal of obstetrics and gynecology. 2023;228(3):270-5. e4.
  87. Forabosco A, Sforza C. Establishment of ovarian reserve: a quantitative morphometric study of the developing human ovary. Fertility and Sterility. 2007;88(3):675-83.
  88. Feng L, Lingling E, Liu H. The effects of separating inferior alveolar neurovascular bundles on osteogenesis of tissue-engineered bone and vascularization. Biomedical Papers. 2015;159(4):637-41.
  89. McKey J, Bunce C, Batchvarov IS, Ornitz DM, Capel B. Neural crest-derived neurons invade the ovary but not the testis during mouse gonad development. Proceedings of the National Academy of Sciences. 2019;116(12):5570-5.
  90. Uchida S. Sympathetic regulation of estradiol secretion from the ovary. Autonomic Neuroscience. 2015;187:27-35.
  91. Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. 2004;428(6979):145-50.
  92. Wagner M, Yoshihara M, Douagi I, Damdimopoulos A, Panula S, Petropoulos S, et al. Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells. Nature communications. 2020;11(1):1147.
  93. Alberico H, Fleischmann Z, Bobbitt T, Takai Y, Ishihara O, Seki H, et al. Workflow optimization for identification of female germline or oogonial stem cells in human ovarian cortex using single-cell RNA sequence analysis. Stem Cells. 2022;40(5):523-36.
  94. Wu M, Lu Z, Zhu Q, Ma L, Xue L, Li Y, et al. DDX04+ stem cells in the ovaries of postmenopausal women: existence and differentiation potential. Stem Cells. 2022;40(1):88-101.
  95. Bhartiya D, Sharma D. Ovary does harbor stem cells-size of the cells matter! Journal of ovarian research. 2020;13(1):1-3.
  96. Mirzaeian L, Eivazkhani F, Saber M, Moini A, Esfandiari F, Valojerdi MR, et al. In-vivo oogenesis of oogonial and mesenchymal stem cells seeded in transplanted ovarian extracellular matrix. Journal of Ovarian Research. 2023;16(1):1-17.
  97. Silvestris E, D’oronzo S, Cafforio P, Kardhashi A, Dellino M, Cormio G. In vitro generation of oocytes from ovarian stem cells (OSCs): in search of major evidence. International Journal of Molecular Sciences. 2019;20(24):6225.
  98. Saber M, Tavakol P, Esfandiari F. Isolation of female germline stem cells from mouse and human ovaries by differential adhesion. International Journal of Cell Biology. 2022;2022.
  99. 99Guo K, Li C-h, Wang X-y, He D-j, Zheng P. Germ stem cells are active in postnatal mouse ovary under physiological conditions. MHR: Basic science of reproductive medicine. 2016;22(5):316-28.
  100. Wang N, Satirapod C, Ohguchi Y, Park E-S, Woods DC, Tilly JL. Genetic studies in mice directly link oocytes produced during adulthood to ovarian function and natural fertility. Scientific Reports. 2017;7(1):10011.
  101. Martin JJ, Woods DC, Tilly JL. Implications and current limitations of oogenesis from female germline or oogonial stem cells in adult mammalian ovaries. Cells. 2019;8(2):93.
  102. Silvestris E, Cafforio P, D’Oronzo S, Felici C, Silvestris F, Loverro G. In vitro differentiation of human oocyte-like cells from oogonial stem cells: single-cell isolation and molecular characterization. Human Reproduction. 2018;33(3):464-73.
  103. Herraiz S, Romeu M, Buigues A, Martínez S, Díaz-García C, Gómez-Seguí I, et al. Autologous stem cell ovarian transplantation to increase reproductive potential in patients who are poor responders. Fertility and sterility. 2018;110(3):496-505. e1.
  104. Gupta S, Lodha P, Karthick MS, Tandulwadkar SR. Role of autologous bone marrow-derived stem cell therapy for follicular recruitment in premature ovarian insufficiency: review of literature and a case report of world's first baby with ovarian autologous stem cell therapy in a perimenopausal woman of age 45 year. Journal of Human Reproductive Sciences. 2018;11(2):125.
  105. White YA, Woods DC, Takai Y, Ishihara O, Seki H, Tilly JL. Oocyte formation by mitotically active germ cells purified from ovaries of reproductive-age women. Nature medicine. 2012;18(3):413-21.
  106. Leonel ECR. Innovations for Optimizing Fertility and Ovarian Functionality in Female Cancer Patients. Medical Research Archives. 2022;10(10).
  107. Virant-Klun I, Zech N, Rožman P, Vogler A, Cvjetičanin B, Klemenc P, et al. Putative stem cells with an embryonic character isolated from the ovarian surface epithelium of women with no naturally present follicles and oocytes. Differentiation. 2008;76(8):843-56.
  108. Bhartiya D, Parte S, Patel H, Anand S, Sriraman K, Gunjal P. Pluripotent very small embryonic-like stem cells in adult mammalian gonads. Adult stem cell therapies: alternatives to plasticity: Springer; 2014. p. 191-209.
  109. Ratajczak MZ, Ratajczak J, Suszynska M, Miller DM, Kucia M, Shin D-M. A novel view of the adult stem cell compartment from the perspective of a quiescent population of very small embryonic-like stem cells. Circulation Research. 2017;120(1):166-78.
  110. Ganguly R, Metkari S, Bhartiya Dynamics of bone marrow VSELs and HSCs in response to treatment with gonadotropin and steroid hormones, during pregnancy and evidence to support their asymmetric/symmetric cell divisions. Stem Cell Reviews and Reports. 2018;14(1):110-24.
  111. Da Broi M, Giorgi V, Wang F, Keefe D, Albertini D, Navarro P. Influence of follicular fluid and cumulus cells on oocyte quality: clinical implications. Journal of assisted reproduction and genetics. 2018;35(5):735-51.
  112. Eppig JJ, Schultz RM, O'Brien M, Chesnel Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes. Developmental biology. 1994;164(1):1-9.
  113. Brinca AT, Ramalhinho AC, Sousa Â, Oliani AH, Breitenfeld L, Passarinha LA, et al. Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome. Biomedicines. 2022;10(6):1254.
  114. Pla I, Sanchez A, Pors SE, Pawlowski K, Appelqvist R, Sahlin KB, et al. Proteome of fluid from human ovarian small antral follicles reveals insights in folliculogenesis and oocyte maturation. Human Reproduction. 2021;36(3):756-70.
  115. Schallmoser A, Einenkel R, Färber C, Sänger N. In vitro growth (IVG) of human ovarian follicles in frozen thawed ovarian cortex tissue culture supplemented with follicular fluid under hypoxic conditions. 2022.
  116. Von Wald T, Monisova Y, Hacker MR, Yoo SW, Penzias AS, Reindollar RR, et al. Age-related variations in follicular apolipoproteins may influence human oocyte maturation and fertility potential. Fertility and sterility. 2010;93(7):2354-61.
  117. Moreno JM, Núñez MJ, Quinonero 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. Fertility and sterility. 2015;104(4):1037-46. e1.
  118. Liu N, Ma Y, Li R, Jin H, Li M, Huang X, et al. Comparison of follicular fluid amphiregulin and EGF concentrations in patients undergoing IVF with different stimulation protocols. Endocrine. 2012;42(3):708-16.
  119. Chattopadhayay R, Ganesh A, Samanta J, Jana S, Chakravarty B, Chaudhury K. Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecologic and obstetric investigation. 2010;69(3):197-202.
  120. Prieto L, Quesada JF, Cambero O, Pacheco A, Pellicer A, Codoceo R, et al. Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis. Fertility and sterility. 2012;98(1):126-30.
  121. Takeo S, Kimura K, Shirasuna K, Kuwayama T, Iwata H. Age-associated deterioration in follicular fluid induces a decline in bovine oocyte quality. Reproduction, Fertility and Development. 2017;29(4):759-67.
  122. Ban Y, Ran H, Chen Y, Ma L. Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study. Journal of ovarian research. 2021;14(1):1-10.
  123. O'gorman A, Wallace M, Cottell E, Gibney M, McAuliffe F, Wingfield M, et al. Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence. Reproduction. 2013;146(4):389-95.
  124. Sun Z, Wu H, Lian F, Zhang X, Pang C, Guo Y, et al. Human follicular fluid metabolomics study of follicular development and oocyte quality. Chromatographia. 2017;80(6):901-9.
  125. Luti S, Fiaschi T, Magherini F, Modesti PA, Piomboni P, Governini L, et al. Relationship between the metabolic and lipid profile in follicular fluid of women undergoing in vitro fertilization. Molecular Reproduction and Development. 2020;87(9):986-97.
  126. Carbone M, Tatone C, Monache SD, Marci R, Caserta D, Colonna R, et al. Antioxidant enzymatic defences in human follicular fluid: characterization and age‐dependent changes. MHR: Basic science of reproductive medicine. 2003;9(11):639-43.
  127. Lambrinoudaki IV, Augoulea A, Christodoulakos GE, Economou EV, Kaparos G, Kontoravdis A, et al. Measurable serum markers of oxidative stress response in women with endometriosis. Fertility and sterility. 2009;91(1):46-50.
  128. Luddi A, Governini L, Capaldo A, Campanella G, De Leo V, Piomboni P, et al. Characterization of the age-dependent changes in antioxidant defenses and protein’s sulfhydryl/carbonyl stress in human follicular fluid. Antioxidants. 2020;9(10):927.
  129. Agarwal A, Gupta S, Sharma R. Oxidative stress and its implications in female infertility–a clinician's perspective. Reproductive biomedicine online. 2005;11(5):641-50.
  130. Oral O, Kutlu T, Aksoy E, Fıçıcıoğlu C, Uslu H, Tuğrul S. The effects of oxidative stress on outcomes of assisted reproductive techniques. Journal of assisted reproduction and genetics. 2006;23(2):81-5.
  131. Sasaki H, Hamatani T, Kamijo S, Iwai M, Kobanawa M, Ogawa S, et al. Impact of oxidative stress on age-associated decline in oocyte developmental competence. Frontiers in endocrinology. 2019;10:811.
  132. Igarashi H, Takahashi T, Nagase S. Oocyte aging underlies female reproductive aging: biological mechanisms and therapeutic strategies. Reproductive medicine and biology. 2015;14(4):159-69.
  133. Debbarh H, Louanjli N, Aboulmaouahib S, Jamil M, Ahbbas L, Kaarouch I, et al. Antioxidant activities and lipid peroxidation status in human follicular fluid: age-dependent change. Zygote. 2021;29(6):490-4.
  134. Gongadashetti K, Gupta P, Dada R, Malhotra N. Follicular fluid oxidative stress biomarkers and ART outcomes in PCOS women undergoing in vitro fertilization: A cross-sectional study. International Journal of Reproductive BioMedicine. 2021;19(5):449.
  135. Sun Z, Chang H-M, Wang A, Song J, Zhang X, Guo J, et al. Identification of potential metabolic biomarkers of polycystic ovary syndrome in follicular fluid by SWATH mass spectrometry. Reproductive Biology and Endocrinology. 2019;17(1):1-10.
  136. Liu L, Yin T-l, Chen Y, Li Y, Yin L, Ding J, et al. Follicular dynamics of glycerophospholipid and sphingolipid metabolisms in polycystic ovary syndrome patients. The Journal of steroid biochemistry and molecular biology. 2019;185:142-9.
  137. Cordeiro FB, Cataldi TR, de Souza BZ, Rochetti RC, Fraietta R, Labate CA, et al. Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome. Metabolomics. 2018;14(4):1-11.
  138. Lucki NC, Sewer MB. The interplay between bioactive sphingolipids and steroid hormones. Steroids. 2010;75(6):390-9.
  139. Li S, Qi J, Tao Y, Zhu Q, Huang R, Liao Y, et al. Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients. Reproduction. 2020;159(2):159-69.
  140. Yang J, Li Y, Li S, Zhang Y, Feng R, Huang R, et al. Metabolic signatures in human follicular fluid identify lysophosphatidylcholine as a predictor of follicular development. Communications Biology. 2022;5(1):1-11.
  141. Jóźwik M, Jóźwik M, Milewska AJ, Battaglia FC, Jóźwik M. Competitive inhibition of amino acid transport in human preovulatory ovarian follicles. Systems Biology in Reproductive Medicine. 2017;63(5):311-7.
  142. Chen X, Lu T, Wang X, Sun X, Zhang J, Zhou K, et al. Metabolic alterations associated with polycystic ovary syndrome: A UPLC Q-Exactive based metabolomic study. Clinica Chimica Acta. 2020;502:280-6.
  143. Bianchi L, Gagliardi A, Landi C, Focarelli R, De Leo V, Luddi A, et al. Protein pathways working in human follicular fluid: the future for tailored IVF? Expert reviews in molecular medicine. 2016;18.
  144. Zamah AM, Hassis ME, Albertolle ME, Williams KE. Proteomic analysis of human follicular fluid from fertile women. Clinical proteomics. 2015;12(1):1-12.
  145. la Cour Poulsen L, Pla I, Sanchez A, Grøndahl ML, Marko-Varga G, Andersen CY, et al. Progressive changes in human follicular fluid composition over the course of ovulation: quantitative proteomic analyses. Molecular and cellular endocrinology. 2019;495:110522.
  146. Zhao H, Zhao Y, Li T, Li M, Li J, Li R, et al. Metabolism alteration in follicular niche: The nexus among intermediary metabolism, mitochondrial function, and classic polycystic ovary syndrome. Free Radical Biology and Medicine. 2015;86:295-307.
  147. Sugiura K, Pendola FL, Eppig JJ. Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Developmental biology. 2005;279(1):20-30.
  148. Zhang Y, Liu L, Yin T-L, Yang J, Xiong C-L. Follicular metabolic changes and effects on oocyte quality in polycystic ovary syndrome patients. Oncotarget. 2017;8(46):80472.
  149. Yang X, Wu R, Qi D, Fu L, Song T, Wang Y, et al. Profile of bile acid metabolomics in the follicular fluid of PCOS patients. Metabolites. 2021;11(12):845.
  150. Yu L, Liu M, Wang Z, Liu T, Liu S, Wang B, et al. Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome. Reproductive Biology and Endocrinology. 2021;19(1):1-11.
  151. Combelles CM. The antral follicle: a microenvironment for oocyte differentiation. International Journal of Developmental Biology. 2013;56(10-11-12):819-31.
  152. Li Z, Zhu Y, Li H, Jiang W, Liu H, Yan J, et al. Leukaemia inhibitory factor in serum and follicular fluid of women with polycystic ovary syndrome and its correlation with IVF outcome. Reproductive BioMedicine Online. 2018;36(4):483-9.
  153. Aghajanova L. Update on the role of leukemia inhibitory factor in assisted reproduction. Current Opinion in Obstetrics and Gynecology. 2010;22(3):213-9.
  154. Basuino¹ L, Silveira CF. Human follicular fluid and effects on reproduction. 2016.
  155. Zhou C-J, Wu S-N, Shen J-P, Wang D-H, Kong X-W, Lu A, et al. The beneficial effects of cumulus cells and oocyte-cumulus cell gap junctions depends on oocyte maturation and fertilization methods in mice. PeerJ. 2016;4:e1761.
  156. Fahiminiya S, Gérard N. Follicular fluid in mammals. Gynecologie, Obstetrique & Fertilite. 2010;38(6):402-4.
  157. Tahajjodi SS, Yazd EF, Agha-Rahimi A, Aflatoonian R, Khalili MA, Mohammadi M, et al. Biological and physiological characteristics of human cumulus cells in adherent culture condition. International Journal of Reproductive BioMedicine. 2020;18(1):1.
  158. Coticchio G, Dal Canto M, Mignini Renzini M, Guglielmo MC, Brambillasca F, Turchi D, et al. Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization. Human reproduction update. 2015;21(4):427-54.
  159. Wigglesworth K, Lee K-B, O’Brien MJ, Peng J, Matzuk MM, Eppig JJ. Bidirectional communication between oocytes and ovarian follicular somatic cells is required for meiotic arrest of mammalian oocytes. Proceedings of the National Academy of Sciences. 2013;110(39):E3723-E9.
  160. Monniaux D. Driving folliculogenesis by the oocyte-somatic cell dialog: Lessons from genetic models. Theriogenology. 2016;86(1):41-53.
  161. Ge L, Sui H-S, Lan G-C, Liu N, Wang J-Z, Tan J-H. Coculture with cumulus cells improves maturation of mouse oocytes denuded of the cumulus oophorus: observations of nuclear and cytoplasmic events. Fertility and Sterility. 2008;90(6):2376-88.
  162. Gilchrist RB, Lane M, Thompson JG. Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Human reproduction update. 2008;14(2):159-77.
  163. FitzHarris G, Siyanov V, Baltz JM. Granulosa cells regulate oocyte intracellular pH against acidosis in preantral follicles by multiple mechanisms. 2007.
  164. Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin 37. Nature. 1997;385(6616):525-9.
  165. Albertini DF, Combelles C, Benecchi E, Carabatsos MJ. Cellular basis for paracrine regulation of ovarian follicle development. Reproduction. 2001;121(5):647-53.
  166. Sutton-McDowall ML, Gilchrist RB, Thompson JG. The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction. 2010;139(4):685.
  167. Shaeib F, Khan SN, Ali I, Thakur M, Saed G, Dai J, et al. The defensive role of cumulus cells against reactive oxygen species insult in metaphase II mouse oocytes. Reproductive Sciences. 2016;23(4):498-507.
  168. Lolicato F, Brouwers JF, de Lest CHv, Wubbolts R, Aardema H, Priore P, et al. The cumulus cell layer protects the bovine maturing oocyte against fatty acid-induced lipotoxicity. Biology of reproduction. 2015;92(1):16, 1-.
  169. Devine PJ, Perreault SD, Luderer U. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biology of reproduction. 2012;86(2):27, 1-10.
  170. Tatemoto H, Sakurai N, Muto N. Protection of porcine oocytes against apoptotic cell death caused by oxidative stress during in vitro maturation: role of cumulus cells. Biology of reproduction. 2000;63(3):805-10.
  171. Keefe D, Kumar M, Kalmbach K. Oocyte competency is the key to embryo potential. Fertility and Sterility. 2015;103(2):317-22.
  172. Lee M-S, Liu C-H, Lee T-H, Wu H-M, Huang C-C, Huang L-S, et al. Association of creatin kinase B and peroxiredoxin 2 expression with age and embryo quality in cumulus cells. Journal of assisted reproduction and genetics. 2010;27(11):629-39.
  173. Hanson BM, Tao X, Zhan Y, Kim JG, Klimczak AM, Herlihy NS, et al. Shorter telomere length of white blood cells is associated with higher rates of aneuploidy among infertile women undergoing in vitro fertilization. Fertility and sterility. 2021;115(4):957-65.
  174. Lara-Molina EE, Franasiak JM, Marin D, Tao X, Díaz-Gimeno P, Florensa M, et al. Cumulus cells have longer telomeres than leukocytes in reproductive-age women. Fertility and sterility. 2020;113(1):217-23.
  175. Morin SJ, Tao X, Marin D, Zhan Y, Landis J, Bedard J, et al. DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation. Aging (Albany NY). 2018;10(12):3761.
  176. Babayev E, Duncan FE. Age-associated changes in cumulus cells and follicular fluid: The local oocyte microenvironment as a determinant of gamete quality. Biology of reproduction. 2022;106(2):351-65.
  177. Lee KS, Joo BS, Na YJ, Yoon MS, Choi OH, Kim WW. Clinical assisted reproduction: cumulus cells apoptosis as an indicator to predict the quality of oocytes and the outcome of IVF–ET. Journal of assisted reproduction and genetics. 2001;18(9):490-8.
  178. Siristatidis CS, Maheshwari A, Vaidakis D, Bhattacharya S. In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction. Cochrane Database of Systematic Reviews. 2018(11).
  179. Lee H-J, Quaas AM, Wright DL, Toth TL, Teixeira JM. In vitro maturation (IVM) of murine and human germinal vesicle (GV)–stage oocytes by coculture with immortalized human fallopian tube epithelial cells. Fertility and sterility. 2011;95(4):1344-8.
  180. Abdel-Ghani MA, Abe Y, Asano T, Hamano S, Suzuki H. Effect of bovine cumulus–oocyte complexes-conditioned medium on in-vitro maturation of canine oocytes. Reproductive medicine and biology. 2011;10(1):43-9.
  181. Chen H-F, Jan P-S, Kuo H-C, Wu F-C, Lan C-W, Huang M-C, et al. Granulosa cells and retinoic acid co-treatment enrich potential germ cells from manually selected Oct4-EGFP expressing human embryonic stem cells. Reproductive biomedicine online. 2014;29(3):319-32.
  182. Qing T, Shi Y, Qin H, Ye X, Wei W, Liu H, et al. Induction of oocyte-like cells from mouse embryonic stem cells by co-culture with ovarian granulosa cells. Differentiation. 2007;75(10):902-11.
Medical Journal of Mashhad university of Medical Sciences
Volume 68, Issue 5
November and December 2025
Pages 1457-1482

Files

Share

How to cite

Statistics