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DOI: 10.47026/2413-4864-2025-2-71-83
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UDC: 611.013.15/.16:577.175.326(07)
BBC: 28.03я73

Zhiznin V.V., Shurygina O.V., Popova O.O., Bachurin A.V., Kutikhin D.Yu.

Molecular mechanisms of oocyte maturation: the role of luteinizing hormone in meiosis regulation

Keywords: oogenesis, meiosis, cumulus cells, cyclic nucleotides (cAMP, cGMP), assisted reproductive technologies, luteinizing hormone

In this review paper, the molecular mechanisms of mammalian oocyte meiotic maturation are considered in detail, with an emphasis on the role of luteinizing hormone and its interaction with signaling pathways regulating cyclic nucleotide levels (cAMP and cGMP). A structured analysis of the key stages of folliculogenesis, the mechanism of meiotic blocking and its removal, as well as the molecular components involved in regulating the permeability of gap junctions between somatic cells and the oocyte is presented. The contribution of various phosphodiesterases, receptors, and peptide mediators to initiation of meiosis is discussed. Special attention is paid to the dual role of the luteinizing hormone: as a trigger for a cascade of intracellular changes in granulosa and cumulus cells, and as an indirect initiator of meiosis resumption in the oocyte. The latest achievements in the field of visualizing and monitoring intracellular signaling events using FRET-sensors and molecular markers are considered. The review differs from previously published similar papers in that it does not limit itself to describing individual signaling components, but builds a holistic model of meiosis regulation, including both classical and recently discovered molecules. Besides, the work examines promising directions of modulating these processes within the framework of assisted reproductive technologies, suggesting potential targets for improving oocytic competence and the success of in vitro fertilization programs.

References

  1. Anderson E., Albertini D.F. Gap junctions between the oocyte and companion follicle cells in the mammalian ovary. J Cell Biol, 1976, vol. 71(2), pp. 680–686. DOI: 10.1083/jcb.71.2.680.
  2. Anderson E., Wilkinson R.F., Lee G. et al. A correlative microscopical analysis of differentiating ovarian follicles of mammals. J Morphol., 1978, vol. 156(3), pp. 339– DOI: 10.1002/jmor.1051560303.
  3. Ashkenazi H., Cao X., Motola S. et al. Epidermal growth factor family members: endogenous mediators of the ovulatory response. Endocrinology, 2005, vol. 146(1), pp. 77– DOI: 10.1210/en.2004-0588.
  4. Bevans C.G., Kordel M., Rhee S.K. et al. Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules. J Biol Chem, 1998, vol. 273(5), pp. 2808–2816. DOI: 10.1074/jbc.273.5.2808.
  5. Chen J., Torcia S., Xie F. et al. Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes. Nat Cell Biol., 2013, vol.15(12), pp. 1415– DOI: 10.1038/ncb2873.
  6. Chen X., Zhou B., Yan J. et al. Epidermal growth factor receptor activation by protein kinase C is necessary for FSH-induced meiotic resumption in porcine cumulus-oocyte complexes. J Endocrinol., 2008, vol. 197(2), pp. 409-419. DOI: 10.1677/JOE-07-0592.
  7. Cho W.K., Stern S., Biggers J.D. Inhibitory effect of dibutyryl cAMP on mouse oocyte maturation in vitro. J Exp Zool, 1974, vol. 187(3), pp. 383– DOI: 10.1002/jez.1401870307.
  8. Conti M., Hsieh M., Zamah A.M. et al. Novel signaling mechanisms in the ovary during oocyte maturation and ovulation. Cell Endocrinol., 2012, vol. 356(1-2), pp. 65–73. DOI: 10.1016/j.mce.2011.11.002.
  9. Dekel N., Beers W.H. Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins. Proc Natl AcadSci USA, 1978, vol. 75(9), pp. 4369– DOI: 10.1073/pnas.75.9.4369.
  10. DiLuigi A., Weitzman V.N., Pace M.C. et al. Meiotic arrest in human oocytes is maintained by a Gs signaling pathway. BiolReprod., 2008, vol. 78(4), pp. 667–672. DOI: 10.1095/biolreprod.107.066019.
  11. Dumesic D.A., Meldrum D.R., Katz-Jaffe M.G. et al. Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health. FertilSteril., 2015, vol. 103(2), pp. 303–316. DOI: 10.1016/j.fertnstert.2014.11.015.
  12. Edson M.A., Nagaraja A.K., Matzuk M.M. The mammalian ovary from genesis to revelation. Endocr Rev., 2009, vol. 30(6), pp. 624–712. DOI: 10.1210/er.2009-0012.
  13. Egbert J.R., Uliasz T.F., Shuhaibar L.C. et al. Luteinizing hormone causes phosphorylation and activation of the cyclic GMP phosphodiesterase PDE5 in rat ovarian follicles, contributing, together with PDE1 activity, to the resumption of meiosis. Reprod., 2016, vol. 94(110), pp. 1–11. DOI: 10.1095/biolreprod.115.135897.
  14. Eppig J.J., O’Brien M., Wigglesworth K. Mammalian oocyte growth and development in vitro. MolReprod, 1996, vol. 44(2), pp. 260–273. DOI: 10.1002/(SICI)1098-2795(199606)44:2<260::AID-MRD17>3.0.CO;2-6.
  15. Eppig J.J., Wigglesworth K., Pendola F.L. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl AcadSci USA, 2002, vol. 99(5), pp. 2890–2894. DOI: 10.1073/pnas.052658699.
  16. Fan H.Y., Liu Z., Shimada M. et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Scienc, 2009, vol. 324(5929), pp. 938–941. DOI: 10.1126/science.1171396.
  17. Flynn M.P., Maizels E.T., Karlsson A.B. et al. Luteinizing hormone receptor activation in ovarian granulosa cells promotes protein kinase A-dependent dephosphorylation of microtubule-associated protein 2D. Endocrinol., 2008, vol. 22, pp. 1695–1710. DOI: 10.1210/me.2007-0457.
  18. Fru K.N., Cherian-Shaw M., Puttabyatappa M. et al. Regulation of granulosa cell proliferation and EGF-like ligands during the periovulatory interval in monkeys. Hum Reprod., 2007, vol. 22(5), pp. 1247–1252. DOI: 10.1093/humrep/del519.
  19. Gilchrist R.B., Luciano A.M., Richani D. et al. Oocyte maturation and quality: role of cyclic nucleotides. Reproduction, 2016, vol. 152(5), pp. 143–157. DOI: 10.1530/REP-15-0606.
  20. Gittens J.E., Kidder G.M. Differential contributions of connexin37 and connexin43 to oogenesis revealed in chimeric reaggregated mouse ovaries. J Cell Sci., 2005, vol. 118(Pt 21), pp. 5071–5078. DOI: 10.1242/jcs.02624.
  21. Horner K., Livera G., Hinckley M. et al. Rodent oocytes express an active adenylyl cyclase required for meiotic arrest. Dev Biol., 2003, vol. 258(2), pp. 385–396. DOI: 10.1016/s0012-1606(03)00134-9.
  22. Hsieh M., Lee D., Panigone S. et al. Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Mol Cell Biol., 2007, vol. 27(5), pp. 1914–1924. DOI: 10.1128/MCB.01919-06.
  23. Hsueh A.J., Kawamura K., Cheng Y. et al. Intraovarian control of early folliculogenesis. Endocr Rev., 2015, vol. 36(1), pp. 1–24. DOI: 10.1210/er.2014-1020.
  24. Hubbard C.J., Terranova P.F. Inhibitory action of cyclic guanosine 5′-phosphoric acid (GMP) on oocyte maturation: dependence on an intact cumulus. , 1982, vol. 26(4), pp. 628–632. DOI: 10.1095/biolreprod26.4.628.
  25. Hubbard C.J. Cyclic AMP changes in the component cells of Graafian follicles: possible influences on maturation in the follicle-enclosed oocytes of hamsters. Dev Biol., 1986, vol. 118(2), pp. 343–351. DOI: 10.1016/0012-1606(86)90003-5.
  26. Hunzicker-Dunn M. Rabbit follicular adenylyl cyclase activity. I. Conditions of assay and gonadotropin sensitivity in granulosa cells and follicle shells. Reprod., 1981, vol. 24, pp. 267–278. DOI: 10.1095/biolreprod24.2.267.
  27. Inoue Y., Miyamoto S., Fukami T. et al. Amphiregulin is much more abundantly expressed than transforming growth factor-alpha and epidermal growth factor in human follicular fluid obtained from patients undergoing in vitro fertilization-embryo transfer. , 2009, vol. 91(4), pp. 1035–1041. DOI: 10.1016/j.fertnstert.2008.01.014.
  28. Jaffe L.A., Egbert J.R. Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle. Annu Rev Physiol., 2017, vol. 79, pp. 237–260. DOI: 10.1146/annurev-physiol-022516-034102.
  29. Jensen J.T., Schwinof K.M., Zelinski-Wooten M.B. et al. Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro. Hum Reprod., 2002, vol. 17(8), pp. 2079–2084. DOI: 10.1093/humrep/17.8.2079.
  30. Jia Z., Wang X. Effects of C-type natriuretic peptide on meiotic arrest and developmental competence of bovine oocyte derived from small and medium follicles. Sci Rep., 2020, vol. 10(1), pp. 18213. DOI: 10.1038/s41598-020-75354-5.
  31. Kanaporis G., Mese G., Valiuniene L. et al. Gap junction channels exhibit connexin-specific permeability to cyclic nucleotides. J Gen Physiol., 2008, vol. 131(4), pp. 293–305. DOI: 10.1085/jgp.200709934.
  32. Kawamura K., Cheng Y., Kawamura N. et al. Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes. Hum Reprod., 2011, vol. 26(11), pp. 3094–3101. DOI: 10.1093/humrep/der282.
  33. Khan S., Ali R.H., Abbasi S. et al. Novel mutations in natriuretic peptide receptor-2 gene underlie acromesomelic dysplasia, type maroteaux. BMC Med Genet., 2012, vol. 13(44). DOI: 10.1186/1471-2350-13-44.
  34. Laforest M.F., Pouliot E., Guéguen L. et al. Fundamental significance of specific phosphodiesterases in the control of spontaneous meiotic resumption in porcine oocytes. MolReprod Dev. 2005, vol. 70(3), pp. 361–372. DOI: 10.1002/mrd.20203.
  35. Li T.Y., Colley D., Barr K.J. et al. Rescue of oogenesis in Cx37-null mutant mice by oocyte-specific replacement with Cx43. J Cell Sci., 2007, vol. 120(23), pp. 4117–4125. DOI: 10.1242/jcs.03488.
  36. Lindbloom S.M., Farmerie T.A., Clay C.M. et al. Potential involvement of EGF-like growth factors and phosphodiesterases in initiation of equine oocyte maturation. AnimReprod Sci., 2008, vol. 103(1-2), pp. 187–192. DOI: 10.1016/j.anireprosci.2007.04.006.
  37. Lyga S., Volpe S., Werthmann R.C. et al. Persistent cAMP Signaling by Internalized LH Receptors in Ovarian Follicles. Endocrinology, 2016, vol. 157(4), pp. 1613–1621. DOI: 10.1210/en.2015-1945. Epub 2016 Feb 1.
  38. Magnusson C., Hillensjö T. Inhibition of maturation and metabolism in rat oocytes by cyclic amp. J Exp Zool, 1977, vol. 201(1), pp. 139–147. DOI: 10.1002/jez.1402010117.
  39. 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, vol. 69(6), pp. 436–449. DOI: 10.1002/jemt.20303.
  40. Masciarelli S., Horner K., Liu C. et al. Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility. J Clin Invest., 2004, vol. 114(2), pp. 196–205. DOI: 10.1172/JCI21804.
  41. Maurice D.H., Haslam R.J. Molecular basis of the synergistic inhibition of platelet function by nitrovasodilators and activators of adenylate cyclase: inhibition of cyclic AMP breakdown by cyclic GMP. MolPharmacol., 1990, vol. 37(5), pp. 671–681.
  42. Mayes M.A., Sirard M.A. Effect of type 3 and type 4 phosphodiesterase inhibitors on the maintenance of bovine oocytes in meiotic arrest. , 2002, vol. 66(1), pp. 180–184. DOI: 10.1095/biolreprod66.1.180.
  43. McGee E.A., Hsueh A.J. Initial and cyclic recruitment of ovarian follicles. , 2000, vol. 21(2), pp. 200–214. DOI: 10.1210/edrv.21.2.0394.
  44. Mehlmann L.M., Jones T.L., Jaffe L.A. Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte. Science, 2002, vol. 297(5585), pp. 1343–1345. DOI: 10.1126/science.1073978.
  45. Messinger S.M., Albertini D.F. Centrosome and microtubule dynamics during meiotic progression in the mouse oocyte. J CellSci., 1991, vol. 100(Pt 2), pp. 289–298. DOI: 10.1242/jcs.100.2.289.
  46. Nogueira D., Albano C., Adriaenssens T. et al. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. BiolReprod., 2003, vol. 69(3), pp. 1042–1052. DOI: 10.1095/biolreprod.103.015982.
  47. Norris R.P., Freudzon M., Mehlmann L.M. et al. Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption. Development, 2008, vol. 135(19), pp. 3229–3238. DOI: 10.1242/dev.025494.
  48. Norris R.P., Freudzon M., Mehlmann L.M. et al. Luteinizing hormone causes MAPK-dependent phosphorylation and closure of Cx43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption. Development, 2008, vol. 135, pp. 3229–3238. DOI: 10.1242/dev.025494.
  49. Norris R.P., Freudzon M., Nikolaev V.O. et al. Epidermal growth factor receptor kinase activity is required for gap junction closure and for part of the decrease in ovarian follicle cGMP in response to LH. Reproduction, 2010, vol. 140(5), pp. 655–662. DOI: 10.1530/REP-10-0288.
  50. Norris R.P., Ratzan W.J., Freudzon M. et al. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development, 2009, vol. 136(11), pp. 1869–1878. DOI: 10.1242/dev.035238.
  51. Park J.Y., Su Y.Q., Ariga M. et al. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science, 2004, vol. 303(5658), pp. 682–684. DOI: 10.1126/science.1092463.
  52. Pedersen T., Peters H. Proposal for a classification of oocytes and follicles in the mouse ovary. J ReprodFertil. 1968, vol. 17(3), pp. 555–557. DOI: 10.1530/jrf.0.0170555.
  53. Ponsioen B., van Zeijl L., Moolenaar W.H. et al. Direct measurement of cyclic AMP diffusion and signaling through connexin43 gap junctional channels. Exp Cell Res., 2007, vol. 313(2), pp. 415–423. DOI: 10.1016/j.yexcr.2006.10.029.
  54. Ratner A. Effects of follicle stimulating hormone and luteinizing hormone upon cyclic AMP and cyclic GMP levels in rat ovaries in vitro. Endocrinology, 1976, vol. 99(6), pp. 1496–1500. DOI: 10.1210/endo-99-6-1496.
  55. Reinhardt R.R., Chin E., Zhou J. et al. Distinctive anatomical patterns of gene expression for cGMP-inhibited cyclic nucleotide phosphodiesterases. J Clin Invest., 1995, vol. 95(4), pp. 1528–1538. DOI: 10.1172/JCI117825.
  56. Richard S., Baltz J.M. Prophase I arrest of mouse oocytes mediated by natriuretic peptide precursor C requires GJA1 (connexin-43) and GJA4 (connexin-37) gap junctions in the antral follicle and cumulus oocyte complex. Reprod., 2014, vol. 90(6), p. 137. DOI: 10.1095/biolreprod.114.118505.
  57. Rodriguez K.F., Couse J.F., Jayes F.L. et al. Insufficient luteinizing hormone-induced intracellular signaling disrupts ovulation in preovulatory follicles lacking estrogen receptor-{beta}. Endocrinology, 2010, vol. 151(6), pp. 2826–2834. DOI: 10.1210/en.2009-1446.
  58. Santiquet N., Papillon-Dion E., Djender N. et al. New elements in the C-type natriuretic peptide signaling pathway inhibiting swine in vitro oocyte meiotic resumption. , 2014, vol. 91(1), p. 16. DOI: 10.1095/biolreprod.113.114132.
  59. Schultz R.M., Montgomery R.R., Belanoff J.R. Regulation of mouse oocyte meiotic maturation: implication of a decrease in oocyte cAMP and protein dephosphorylation in commitment to resume meiosis. Dev Biol., 1983, vol. 97(2), pp. 264– DOI: 10.1016/0012-1606(83)90085-4.
  60. Sekiguchi T., Mizutani T., Yamada K. et al. Expression of epiregulin and amphiregulin in the rat ovary. J MolEndocrinol, 2004, vol. 33(1), pp. 281– DOI: 10.1677/jme.0.0330281.
  61. Sela-Abramovich S., Edry I., Galiani D. et al. Disruption of gap junctional communication within the ovarian follicle induces oocyte maturation. Endocrinology, 2006, vol. 147, pp. 2280–2286. DOI: 10.1210/en.2005-1011.
  62. Shuhaibar L.C., Egbert J.R., Norris R.P. et al. Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles. Proc Natl AcadSci USA, 2015, vol. 112(17), pp. 5527–5532. DOI: 10.1073/pnas.1423598112.
  63. Silber S.J., Kato K., Aoyama N. et al. Intrinsic fertility of human oocytes. , 2017, vol.107(5), pp. 1232–1237. DOI: 10.1016/j.fertnstert.2017.03.014.
  64. Simon A.M., Goodenough D.A., Li E. et al. Female infertility in mice lacking connexin 37. Nature, 1997, vol. 385(6616), pp. 525–529. DOI: 10.1038/385525a0.
  65. Solc P., Schultz R.M., Motlik J. Prophase I arrest and progression to metaphase I in mouse oocytes: comparison of resumption of meiosis and recovery from G2-arrest in somatic cells. Mol Hum Reprod., 2010, vol. 16(9), pp. 654–664. DOI: 10.1093/molehr/gaq034.
  66. Su Y.Q., Wigglesworth K., Pendola F.L. et al. Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse. Endocrinology, 2002, vol. 143(6), pp. 2221–2232. DOI: 10.1210/endo.143.6.8845.
  67. Thomas R.E., Armstrong D.T., Gilchrist R.B. Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation. Dev Biol., 2002, vol. 244(2), pp. 215– DOI: 10.1006/dbio.2002.0609.
  68. Tsafriri A., Chun S.Y., Zhang R. et al. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol., 1996, vol. 178(2), pp. 393– DOI: 10.1006/dbio.1996.0226.
  69. Tsafriri A., Lindner H.R., Zor U. et al. In-vitro induction of meiotic division in follicle-enclosed rat oocytes by LH, cyclic AMP and prostaglandin E 2 . J ReprodFertil., 1972, vol. 31(1), pp. 39–50. DOI: 10.1530/jrf.0.0310039.
  70. Törnell J., Billig H., Hillensjö T. Regulation of oocyte maturation by changes in ovarian levels of cyclic nucleotides. Hum Reprod., 1991, vol. 6(3), pp. 411– DOI: 10.1093/oxfordjournals.humrep.a137351.
  71. Vaccari S., Weeks J.L., Hsieh M. et al. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. BiolReprod., 2009, vol. 81(3), pp. 595–604. doi: 10.1095/biolreprod.109.077768.
  72. Van den Hurk R., Zhao J. Formation of mammalian oocytes and their growth, differentiation and maturation within ovarian follicles. Theriogenology, 2005, vol. 63(6), pp. 1717– DOI: 10.1016/j.theriogenology.2004.08.005.
  73. Wang Y., Li J., Ying Wang C., Yan Kwok A.H. et al. Epidermal growth factor (EGF) receptor ligands in the chicken ovary: I. Evidence for heparin-binding EGF-like growth factor (HB-EGF) as a potential oocyte-derived signal to control granulosa cell proliferation and HB-EGF and kit ligand expression. Endocrinology, 2007, vol. 148(7), pp. 3426–3440. DOI: 10.1210/en.2006-1383.
  74. Wiersma A., Hirsch B., Tsafriri A. et al. Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents. J Clin Invest., 1998, vol. 102(3), pp. 532– DOI: 10.1172/JCI2566.
  75. Zamah A.M., Hsieh M., Chen J. et al. Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin. Hum Reprod., 2010, vol. 25(10), pp. 2569–2578. DOI: 10.1093/humrep/deq212.
  76. Zhang M., Su Y.Q., Sugiura K. et al. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science, 2010, vol. 330(6002), pp. 366–369. DOI: 10.1126/science.
  77. Zhang Q., Liu D., Zhang M. et al. Effects of brain-derived neurotrophic factor on oocyte maturation and embryonic development in a rat model of polycystic ovary syndrome. ReprodFertil Dev., 2016, vol. 28(12), pp. 1904–1915. DOI: 10.1071/RD15131.

About authors

Zhiznin Vasily V.
Post-Graduate Student, Department of Histology and Embryology, Samara State Medical University, Russia, Samara; Head of the Embryology Laboratory , «Family Medicine Center» JSC, Russia, Magnitogorsk (4uter2@mail.ru; ORCID: https://orcid.org/0000-0002-0604-881X)
Shurygina Oksana V.
Doctor of Medical Sciences, Professor, Department of Histology and Embryology, Department of Reproductive Medicine, Clinical Embryology and Genetics, Samara State Medical University; Head of the Embryological Laboratory, Clinical Hospital IDK "Mother and Child", Russia, Samara (oks-shurygina@yandex.ru; ORCID: https://orcid.org/0000-0002-3903-4350)
Popova Olga O.
a Competitor of Scientific Degree of Medical Sciences Candidate, Department of Histology and Embryology, Samara State Medical University, Russia, Samara (popovaoo@outlook.com; ORCID: https://orcid.org/0000-0002-8681-8844)
Bachurin Alexey V.
a Competitor of Scientific Degree of Medical Sciences Candidate, Department of Histology and Embryology, Samara State Medical University, Russia, Samara (bachurin.a.v@gmail.com; ORCID: https://orcid.org/0000-0002-3768-7657)
Kutikhin Dmitry Yu.
Resident, Department of Histology and Embryology, Samara State Medical University, Russia, Samara (Lol.gor.2017@mail.ru; ORCID: https://orcid.org/0000-0001-6944-8565)

Article link

Zhiznin V.V., Shurygina O.V., Popova O.O., Bachurin A.V., Kutikhin D.Yu. Molecular mechanisms of oocyte maturation: the role of luteinizing hormone in meiosis regulation [Electronic resource] // Acta medica Eurasica. – 2025. – №2. P. 71-83. – URL: https://acta-medica-eurasica.ru/en/single/2025/2/9/. DOI: 10.47026/2413-4864-2025-2-71-83.

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