About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
About
The Journal "Obstetrics and Gynecology"Journal HistoryAims and ScopePolicies on Conflict of Interest, Human and Animal Rights, and Informed ConsentEditorial ProcessData sharing statementAdvertising PolicyThe Process for Handling Cases Requiring Corrections, Retractions, and Editorial Expressions of ConcernEditorial BoardEditorial CounsilInformation for ProfessionalsNewsContacts
ArchiveEthical StandardsSubscription
For authors
InstructionsInformed consent policyContract offerEASE GuidelinesICJME CriteriaWAME Recommendations on ChatGPT and Chatbots in Relation to Scholarly Publications
Reviewing
Procedure for reviewingReviewers 2023-2024
Logout
Obstetrics and Gynegology2024№1
Extracellular vesicles derived from multipotent...

Extracellular vesicles derived from multipotent mesenchymal stromal cells: pathogenetic rationale for therapeutic use

DOI
https://dx.doi.org/10.18565/aig.2023.239

Martirosyan Ya.O., Kadaeva A.I., Silachev D.N., Nazarenko T.A., Matveeva P.V.

Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia

The article presents a review of scientific studies of modern views on folliculogenesis and its regulation. The review covers the possibilities and prospects for the use of cell therapy in reproductive medicine, as well as possible mechanisms of influence of stem cells and their extracellular vesicles on the mechanisms of follicle recruitment. The prospects of using targeted agents in the treatment of primary ovarian insufficiency are explained by the fact that most of the ovarian primordial follicles remain dormant and inactive throughout a woman’s life. The experimental studies made it possible to identify the main signaling pathways involved in the regulation of early folliculogenesis and oogenesis. After studying the regulation of the activity of the key signaling pathways, it will be possible to develop targets in order to influence the gonadotropin-independent phase of follicle growth and to prevent such disorders of the reproductive system as primary ovarian insufficiency and age-associated decrease in the quality and quantity of oocytes. 
The article presents the analysis of the literature data and describes the possible mechanisms of the effect of cell therapy on the ovarian reserve. The review includes the data of foreign articles published in databases eLibrary.ru and PubMed on this issue.  
Conclusion: The presented information on the ways of influence of extracellular vesicles shows the prospects for the treatment of infertility in the complex patient population. It is necessary to continue research into the mechanisms of functioning and application of extracellular vesicles for expanding therapeutic options. 

Authors’ contributions: Martirosyan Ya.O., Kadaeva A.I., Silachev D.N., Nazarenko T.A., Matveeva P.V. – developing the design of the study, obtaining data for analysis, review of publications on the issue of the article, analysis of the obtained data, writing the text of the article.
Conflicts of interest: Authors declare lack of the possible conflicts of interests.
Funding: The study was carried out within the framework of state assignment “Solving the problem of infertility in modern conditions by developing a clinical and diagnostic model of infertile marriage and using innovative technologies in assisted reproduction programs”.
For citation: Martirosyan Ya.O., Kadaeva A.I., Silachev D.N., Nazarenko T.A., Matveeva P.V.  Extracellular vesicles derived from multipotent mesenchymal stromal cells: pathogenetic rationale for therapeutic use.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2024; (1): 26-33 (in Russian)
https://dx.doi.org/10.18565/aig.2023.239

Keywords

decreased ovarian reserve
primary ovarian insufficiency
extracellular vesicles
IVF
IVF/ICSI
intraovarian injection
multipotent mesenchymal stromal cells
Full text (in Russian)

References

  1. De Vos M., Devroey P., Fauser B.C. Primary ovarian insufficiency. Lancet. 2010; 376(9744): 911-21. https://dx.doi.org/10.1016/S0140-6736(10)60355-8.
  2. Golezar S., Ramezani Tehrani F., Khazaei S., Ebadi A., Keshavarz Z. The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric. 2019; 22(4): 403-11. https://dx.doi.org/10.1080/13697137.2019.1574738.
  3. Sydsjö G., Bladh M., Rindeborn K., Hammar M., Rodriguez-Martinez H.,Nedstrand E. Being born preterm or with low weight implies a risk of infertility and premature loss of ovarian function; a national register study. Ups. J. Med. Sci. 2020; 125(3): 235-9. https:/dx.doi.org/10.1080/03009734.2020.1770380.
  4. Akande R.O., Ibrahim Y. Genetics of primary ovarian insufficiency. Clin. Obstet. Gynecol. 2020;63(4):687-705. https://dx.doi.org/10.1097/GRF.0000000000000575.
  5. Wang H., Chen H., Qin Y., Shi Z., Zhao X., Xu J. et al. Risks associated with premature ovarian failure in Han Chinese women. Reprod. Biomed. Online. 2015; 30(4): 401-7. https://dx.doi.org/10.1016/j.rbmo.2014.12.013.
  6. Oftedal B.E., Wolff A.S.B. New era of therapy for endocrine autoimmune disorders. Scand. J. Immunol. 2020; 92(5): e12961. https://dx.doi.org/10.1111/sji.12961.
  7. Beitl K., Rosta K., Poetsch N., Seifried M., Mayrhofer D., Soliman B. et al.Autoimmunological serum parameters and bone mass density in premature ovarian insufficiency: a retrospective cohort study. Arch. Gynecol. Obstet. 2021; 303(4): 1109-15. https://dx.doi.org/10.1007/s00404-020-05860-4.
  8. Bahrehbar K., Rezazadeh Valojerdi M., Esdiari F., Fathi R., Hassani S.N., Baharvand H. Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure. World J. Stem. Cells. 2020; 12(8): 857-78. https://dx.doi.org/10.4252/wjsc.v12.i8.857.
  9. 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. Hum. Reprod. 2018; 33(3): 464-73. https://dx.doi.org/10.1093/humrep/dex377.
  10. Stimpfel M., Skutella T., Cvjeticanin B., Meznaric M., Dovc P., Novakovic S. et al. Isolation, characterization and differentiation of cells expressing pluripotent/multipotent markers from adult human ovaries. Cell Tissue Res. 2013; 354(2): 593-607. https://dx.doi.org/10.1007/s00441-013-1677-8.
  11. Johnson J., Bagley J., Skaznik-Wikiel M., Lee H.J., Adams G.B., Niikura Y. et al. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005; 122(2): 303-15.https://dx.doi.org/10.1016/j.cell.2005.06.031.
  12. Esmaeilian Y., Atalay A., Erdemli E. Putative germline and pluripotent stem cells in adult mouse ovary and their in vitro differentiation potential into oocyte-like and somatic cells. Zygote. 2017;25(3):358-75. https://dx.doi.org/10.1017/S0967199417000235.
  13. Zhang H., Liu L., Li X., Busayavalasa K., Shen Y., Hovatta O. et al. Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice. Proc. Natl. Acad. Sci. USA. 2014; 111(50): 17983-8. https://dx.doi.org/10.1073/pnas.1421047111.
  14. Begum S., Papaioannou V.E., Gosden R.G. The oocyte population is not renewed in transplanted or irradiated adult ovaries. Hum. Reprod. 2008; 23(10): 2326-30. https://dx.doi.org/10.1093/humrep/den249.
  15. Liu Y., Wu C., Lyu Q., Yang D., Albertini D.F., Keefe D.L. et al. Germline stem cells and neo-oogenesis in the adult human ovary. Dev. Biol. 2007; 306(1): 112-20. https://dx.doi.org/10.1016/j.ydbio.2007.03.006.
  16. Seok J., Park H., Choi J.H., Lim J.Y., Kim K.G., Kim G.J. Placenta-derived mesenchymal stem cells restore the ovary function in an ovariectomized rat model via an antioxidant effect. Antioxidants (Basel). 2020; 9(7): 591.https:/dx.doi.org/10.3390/antiox9070591.
  17. Matsuzaki S., Pankhurst M.W. Hyperactivation of dormant primordial follicles in ovarian endometrioma patients. Reproduction. 2020; 160(6): R145-R153. https://dx.doi.org/10.1530/REP-20-0265.
  18. Zhao F., Lan Y., Chen T., Xin Z., Liang Y., Li Y. et al. Live birth rate comparison of three controlled ovarian stimulation protocols for in vitro fertilization-embryo transfer in patients with diminished ovarian reserve after endometrioma cystectomy: a retrospective study. J. Ovarian Res. 2020; 13(1): 23.https://dx.doi.org/10.1186/s13048-020-00622-x.
  19. Hanson B.M., Tao X., Zhan Y., Jenkins T.G., Morin S.J., Scott R.T., Seli E.U. Young women with poor ovarian response exhibit epigenetic age acceleration based on evaluation of white blood cells using a DNA methylation-derived age prediction model. Hum. Reprod. 2020; 35(11): 2579-88.https://dx.doi.org/10.1093/humrep/deaa206.
  20. Nippita T.A., Baber R.J. Premature ovarian failure: a review. Climacteric. 2007;10(1):11-22. https://dx.doi.org/10.1080/13697130601135672.
  21. Gersak K., Meden-Vrtovec H., Peterlin B. Fragile X premutation in women with sporadic premature ovarian failure in Slovenia. Hum. Reprod. 2003; 18(8): 1637-40. https://dx.doi.org/10.1093/humrep/deg327.
  22. Conway G.S. Premature ovarian failure. Br. Med. Bull. 2000; 56(3): 643-9. https://dx.doi.org/10.1258/0007142001903445.
  23. Laissue P., Christin-Maitre S., Touraine P., Kuttenn F., Ritvos O., Aittomaki K. et al. Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur. J. Endocrinol. 2006; 154(5): 739-44.https://dx.doi.org/10.1530/eje.1.02135.
  24. Crisponi L., Deiana M., Loi A., Chiappe F., Uda M., Amati P. et al. The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat. Genet. 2001; 27(2): 159-66.https://dx.doi.org/10.1038/84781.
  25. Aittomäki K., Lucena J.L., Pakarinen P., Sistonen P., Tapanainen J., Gromoll J. et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995; 82(6): 959-68.https://dx.doi.org/10.1016/0092-8674(95)90275-9.
  26. He W.B., Banerjee S., Meng L.L., Du J., Gong F., Huang H. et al. Whole-exome sequencing identifies a homozygous donor splice-site mutation in STAG3 that causes primary ovarian insufficiency. Clin. Genet. 2018; 93(2): 340-4.https://dx.doi.org/10.1111/cge.13034.
  27. Zhang Y.X., Li H.Y., He W.B., Tu C., Du J., Li W. et al. XRCC2 mutation causes premature ovarian insufficiency as well as non-obstructive azoospermia in humans. Clin. Genet. 2019; 95(3): 442-3. https://dx.doi.org/10.1111/cge.13475.
  28. Zhang Y.X., He W.B., Xiao W.J., Meng L.L., Tan C., Du J. et al. Novel loss-of-function mutation in MCM8 causes premature ovarian insufficiency. Mol. Genet. Genomic Med. 2020; 8(4): e1165. https://dx.doi.org/10.1002/mgg3.1165.
  29. Bouilly J., Beau I., Barraud S., Bernard V., Azibi K., Fagart J. et al. Identification of multiple gene mutations accounts for a new genetic architecture of primary ovarian insufficiency. J. Clin. Endocrinol. Metab. 2016; 101(12): 4541-50. https://dx.doi.org/10.1210/jc.2016-2152.
  30. Jaillard S., Bell K., Akloul L., Walton K., McElreavy K., Stocker W.A. et al. New insights into the genetic basis of premature ovarian insufficiency: novel causative variants and candidate genes revealed by genomic sequencing. Maturitas. 2020; 141: 9-19. https://dx.doi.org/10.1016/j.maturitas.2020.06.004.
  31. Heddar A., Ogur C., Da Costa S., Braham I., Billaud-Rist L., Findikli N. et al. Genetic landscape of a large cohort of Primary Ovarian Insufficiency: New genes and pathways and implications for personalized medicine. EBioMedicine. 2022; 84: 104246. https://dx.doi.org/10.1016/j.ebiom.2022.104246.
  32. Ellwanger K., Becker E., Kienes I., Sowa A., Postma Y., Cardona Gloria Y. et al. The NLR family pyrin domain-containing 11 protein contributes to the regulation of inflammatory signaling. J. Biol. Chem. 2018; 293(8): 2701-10. https://dx.doi.org/10.1074/jbc.RA117.000152.
  33. Hustedt N., Saito Y., Zimmermann M., Álvarez-Quilón A., Setiaputra D., Adam S. et al. Control of homologous recombination by the HROB-MCM8-MCM9 pathway. Genes Dev. 2019; 33(19-20): 1397-415. https://dx.doi.org/10.1101/gad.329508.119.
  34. Zhang Y., Xu X., Hu M., Wang X., Cheng H., Zhou R. SPATA33 is an autophagy mediator for cargo selectivity in germline mitophagy. Cell Death Differ. 2021; 28(3): 1076-90. https://dx.doi.org/10.1038/ s41418-020-00638-2.
  35. Kato Y., Iwamori T., Ninomiya Y., Kohda T., Miyashita J., Sato M., Saga Y. ELAVL2-directed RNA regulatory network drives the formation of quiescent primordial follicles. EMBO Rep. 2019; 20(12): e48251.https://dx.doi.org/10.15252/embr.201948251.
  36. Wang X., Zhang X., Dang Y., Li D., Lu G., Chan W.Y. et al. Long noncoding RNA HCP5 participates in premature ovarian insufficiency by transcriptionally regulating MSH5 and DNA damage repair via YB1. Nucleic Acids Res. 2020; 48(8): 4480-91. https://dx.doi.org/10.1093/nar/gkaa127.
  37. Lu X., Cui J., Cui L., Luo Q., Cao Q., Yuan W., Zhang H. The effects of human umbilical cord-derived mesenchymal stem cell transplantation on endometrial receptivity are associated with Th1/Th2 balance change and uNK cell expression of uterine in autoimmune premature ovarian failure mice. Stem Cell Res. Ther. 2019;10(1): 214. https://dx.doi.org/10.1186/s13287-019-1313-y.
  38. Zheng Q., Fu X., Jiang J., Zhang N., Zou L., Wang W. et al. Umbilical cord mesenchymal stem cell transplantation prevents chemotherapy-induced ovarian failure via the NGF/TrkA pathway in rats. Biomed. Res. Int. 2019; 2019: 6539294. https://dx.doi.org/10.1155/2019/6539294.
  39. Jankowska K. Premature ovarian failure. Menopauzalny. 2017; 16(2): 51-6. https://dx.doi.org/10.5114/pm.2017.68592.
  40. Ding L., Yan G., Wang B., Xu L., Gu Y., Ru T. et al. Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility. Sci. China Life Sci. 2018; 61(12): 1554-65.https://dx.doi.org/10.1007/s11427-017-9272-2.
  41. Yin N., Wu C., Qiu J., Zhang Y., Bo L., Xu Y. et al. Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28- T cells. Stem Cell Res. Ther. 2020; 11(1): 49.https://dx.doi.org/10.1186/s13287-019-1537-x.
  42. Zhang H., Luo Q., Lu X., Yin N., Zhou D., Zhang L. et al. Effects of hPMSCs on granulosa cell apoptosis and AMH expression and their role in the restoration of ovary function in premature ovarian failure mice. Stem Cell Res. Ther. 2018; 9(1): 20. https://dx.doi.org/10.1186/s13287-017-0745-5.
  43. Zhao Y., Ma J., Yi P., Wu J., Zhao F., Tu W. et al. Human umbilical cord mesenchymal stem cells restore the ovarian metabolome and rescue premature ovarian insufficiency in mice. Stem Cell Res. Ther. 2020; 11(11): 466.https://dx.doi.org/10.1186/s13287-020-01972-5.
  44. Feng X., Ling L., Zhang W., Liu X., Wang Y., Luo Y., Xiong Z. Effects of human amnion-derived mesenchymal stem cell (hAD-MSC) transplantation in situ on primary ovarian insufficiency in SD rats. Reprod. Sci. 2020; 27(7): 1502-12. https://dx.doi.org/10.1007/s43032-020-00147-0.
  45. Herraiz S., Buigues A., Díaz-García C., Romeu M., Martínez S., Gómez-Seguí I. et al. Fertility rescue and ovarian follicle growth promotion by bone marrow stem cell infusion. Fertil. Steril. 2018; 109(5): 908-18.e2.https://dx.doi.org/10.1016/j.fertnstert.2018.01.004.
  46. Yoon S.Y., Yoon J.A., Park M., Shin E.Y., Jung S., Lee J.E. et al. Recovery of ovarian function by human embryonic stem cell-derived mesenchymal stem cells in cisplatin-induced premature ovarian failure in mice. Stem Cell Res. Ther. 2020; 11(1): 255. https://dx.doi.org/10.1186/s13287-020-01769-6.
  47. Lu X., Bao H., Cui L., Zhu W., Zhang L., Xu Z. et al. hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway. Stem Cell Res Ther. 2020; 11(1): 268. https://dx.doi.org/10.1186/s13287-020-01784-7.
  48. Cui L., Bao H., Liu Z., Man X., Liu H., Hou Y. et al. hUMSCs regulate the differentiation of ovarian stromal cells via TGF-beta(1)/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats. Stem Cell Res. Ther. 11(1): 386. https://dx.doi.org/10.1186/s13287-020-01904-3.
  49. Liu J., Zhang H., Zhang Y., Li N., Wen Y., Cao F. et al. Homing and restorative effects of bone marrow-derived mesenchymal stem cells on cisplatin injured ovaries in rats. Mol. Cells. 2014; 37(8): 865-72. https://dx.doi.org/10.14348/molcells.2014.0145.
  50. Besikcioglu H.E., Sarıbas G.S., Ozogul C., Tiryaki M., Kilic S., Pınarlı F.A. et al. Determination of the effects of bone marrow derived mesenchymal stem cells and ovarian stromal stem cells on follicular maturation in cyclophosphamide induced ovarian failure in rats. Taiwan. J. Obstet. Gynecol. 2019; 58: 53-9. https://dx.doi.org/10.1016/j.tjog.2018.11.010.
  51. Shen J., Cao D., Sun J.L. Ability of human umbilical cord mesenchymal stem cells to repair chemotherapy-induced premature ovarian failure. World J. Stem Cells. 2019; 12: 277-87. https://dx.doi.org/10.4252/wjsc.v12.i4.277.
  52. Noory P., Navid S., Zanganeh B.M., Talebi A., Borhani-Haghighi M., Gholami K. et al. Human menstrual blood stem cell-derived granulosa cells participate in ovarian follicle formation in a rat model of premature ovarian failure in vivo. Cell. Reprogram. 2019; 21(5): 249-59. https://dx.doi.org/10.1089/cell.2019.002.
  53. Ding C., Zou Q., Wang F., Wu H., Chen R., Lv J. et al. Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor. Stem Cell Res. Ther. 2018; 9(1): 55. https://dx.doi.org/10.1186/s13287-018-0781-9.
  54. Liu R., Zhang X., Fan Z., Wang Y., Yao G., Wan X. et al. Human amniotic mesenchymal stem cells improve the follicular microenvironment to recover ovarian function in premature ovarian failure mice. Stem Cell Res. Ther. 2019; 10(1): 299. https://dx.doi.org/10.1186/s13287-019-1315-9.
  55. Ghadami M., El-Demerdash E., Zhang D., Salama S.A., Binhazim A.A., Archibong A.E. et al. Bone marrow transplantation restores follicular maturation and steroid hormones production in a mouse model for primary ovarian failure. PLoS One. 2012; 7: e32462. https://dx.doi.org/10.1371/journal.pone.0032462.
  56. Yin N., Zhao W., Luo Q., Yuan W., Luan X., Zhang H. Restoring ovarian function with human placenta-derived mesenchymal stem cells in autoimmune-induced premature ovarian failure mice mediated by treg cells and associated cytokines. Reprod Sci 2018; 25(7):1073-82. https://dx.doi.org/10.1177/1933719117732156.
  57. Poulos J. The limited application of stem cells in medicine: a review. Stem Cell Res Ther. 2018; 9(1): 1. https://dx.doi.org/10.1186/s13287-017-0735-7.
  58. Mashouri L., Yousefi H., Aref A.R., Ahadi A.M., Molaei F., Alahari S.K. Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance. Mol. Cancer, 2019; 18(1): 75. https://dx.doi.org/10.1186/S12943-019-0991-5.
  59. Watanabe Y., Tsuchiya A., Terai S. The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future. Clin. Mol. Hepatol. 2021; 27(1): 70-80. https://dx.doi.org/10.3350/cmh.2020.0194.
  60. Hade M.D., Suire C.N., Mossell J., Suo Z. Extracellular vesicles: Emerging frontiers in wound healing. Med. Res. Rev. 2022; 42(6): 2102-25.https://dx.doi.org/10.1002/MED.21918.
  61. Ding C., Zhu L., Shen H., Lu J., Zou Q., Huang C., Li H., Huang B. Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7. Stem Cells. 2020; 38(9): 1137-8. https://dx.doi.org/10.1002/stem.3204.
  62. Sun L., Li D., Song K., Wei J., Yao S., Li Z. et al. Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro. Sci Rep. 2017; 7(1): 2552.https://dx.doi.org/10.1038/s41598-017-02786-x.
  63. Yang Z., Du X., Wang C., Zhang J., Liu C., Li Y., Jiang H. Therapeutic effects of human umbilical cord mesenchymal stem cell-derived microvesicles on premature ovarian insufficiency in mice. Stem Cell Res Ther. 2019; 10(1): 250. https://dx.doi.org/10.1186/s13287-019-1327-5.
  64. Zhang J., Yin H., Jiang H., Du X., Yang Z. The protective effects of human umbilical cord mesenchymal stem cell-derived extracellular vesicles on cisplatin-damaged granulosa cells. Taiwan. J. Obstet. Gynecol. 2020; 59(4): 527-33. https://dx.doi.org/10.1016/j.tjog.2020.05.010.
  65. Deng Z., Wang J., Xiao Y., Li F., Niu L., Liu X. et al. Ultrasound-mediated augmented exosome release from astrocytes alleviates amyloid-β-induced neurotoxicity. Theranostics. 2021; 11(9): 4351-62. https://dx.doi.org/10.7150/thno.52436.
  66. Cai J.H., Sun Y.T., Bao S. HucMSCs-exosomes containing miR-21 promoted estrogen production in ovarian granulosa cells via LATS1-mediated phosphorylation of LOXL2 and YAP. Gen. Comp. Endocrinol. 2022; 321-322: 114015. https://dx.doi.org/10.1016/j.ygcen.2022.114015.
  67. Gao T., Cao Y., Hu M., Du Y. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles carrying MicroRNA-29a improves ovarian function of mice with primary ovarian insufficiency by targeting HMG-Box transcription factor/Wnt/β-Catenin signaling. Dis Markers. 2022; 2022; 5045873.https://dx.doi.org/10.1155/2022/5045873.
  68. Qu Q., Liu L., Cui Y., Liu H., Yi J., Bing W. et al. miR-126-3p containing exosomes derived from human umbilical cord mesenchymal stem cells promote angiogenesis and attenuate ovarian granulosa cell apoptosis in a preclinical rat model of premature ovarian failure. Stem Cell Res. Ther. 2022; 13(1): 352. https://dx.doi.org/10.1186/s13287-022-03056-y.
  69. Li Z., Zhang M., Zheng J., Tian Y., Zhang H., Tan Y. et al. Human umbilical cord mesenchymal stem cell-derived exosomes improve ovarian function and proliferation of premature ovarian insufficiency by regulating the hippo signaling pathway. Front. Endocrinol. (Lausanne). 2021; 12: 711902.https://dx.doi.org/10.3389/fendo.2021.711902.
  70. Lu Y., Wei Y., Shen X., Tong Y., Lu J., Zhang Y. et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles improve ovarian function in rats with primary ovarian insufficiency by carrying miR-145-5p. J. Reprod. Immunol. 2023; 158: 103971. https://dx.doi.org/10.1016/j.jri.2023.103971.

Received 16.10.2023

Accepted 09.01.2024

About the Authors

Yana O. Martirosyan, PhD, obstetrician-gynecologist at Scientific and Clinical Department named after F. Paulsen, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, +7(925) 124-99-99, marti-yana@yandex.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Albina I. Kadaeva, postgraduate student in obstetrics and gynecology, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of the Russian Federation, +7(917)762-82-11, albina.karimovai@mail.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Denis N. Silachev, Dr. Bio. Sci., Head of the Laboratory of Cell Technologies, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, silachevdn@genebee.msu.ru, 117997, Russia, Moscow, Ac. Oparin str., 4.
Tatiana A. Nazarenko, Professor, Dr. Med. Sci., Director of the Institute of Reproductive Medicine, V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, +7(495)531-44-44, t_nazarenko@oparina4.ru, 17997, Russia, Moscow, Ac. Oparin str., 4.
Polina V. Matveeva, student, I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, +7(985)974-74-51,
polina.matveeva00@gmail.ru, 119048, Russia, Moscow, Trubetskaya str., 8/2.

Similar Articles

№6 / 2024
Krylova E.I., Pogosyan M.T.
Missed opportunities for improving the effectiveness of in vitro fertilization programs in patients with diminished ovarian reserve
№12 / 2022
Kirakosyan E.V., Pomerantseva E.A., Pavlovich S.V.
Whole exome sequencing in couples with unexplained infertility (pilot study)
№3 / 2024
Mayasina E.N., Buev Yu.E., Askerov R.A., Yamalyeva N.Sh., Kichigina E.A., Kornilova A.S., Salimov D.F.
Comparative assessment of the efficacy of micronized progesterone medications in the IVF programs
№7 / 2023
Matichin A.A., Kryshen K.L., Faustova N.M, Gushchin Ya.A., Makarova M.N., Reshetnik V.V., Sukhikh G.T., Yudin S.M., Lunin V.G.
Evaluation of the pharmacological activity of a somatostatin-containing protein-based preparation in a model of cyclophosphamide-induced ovarian failure in female mice
№6 / 2024
Martirosyan Ya.O., Nazarenko T.A., Kadaeva A.I., Goryunov K.V., Shevtsova Yu.A.
Activation of ovarian function in patients with diminished ovarian reserve through administration of extracellular vesicles
By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.