[Frontiers In Bioscience, Scholar, 9, 307-318, June 1, 2017]

Nitric oxide signaling during meiotic cell cycle regulation in mammalian oocytes

Meenakshi Tiwari1, Shilpa Prasad1, Ashutosh N. Pandey1, Karuppanan V. Premkumar1, Anima Tripathi1, Anumegha Gupta1, Doddalingaiah R. Chetan1, Pramod K. Yadav1, Tulsidas G. Shrivastav2, Shail K. Chaube1

1Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, U.P., India, 2Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi 110067, India


1. Abstract
2. Introduction
3. NO and meiotic resumption from Diplotene arrest
4. NO and meiotic resumption from Metaphase-II arrest
5. Conclusion
6. Acknowledgment
7. References


Nitric oxide (NO) acts as a major signal molecules and modulate physiology of mammalian oocytes. Ovarian follicles generate large amount of NO through nitric oxide synthase (NOS) pathway to maintain diplotene arrest in preovulatory oocytes. Removal of oocytes from follicular microenvironment or follicular rupture during ovulation disrupt the flow of NO from granulosa cells to the oocyte that results a transient decrease of oocyte cytoplasmic NO level. Decreased NO level reduces cyclic nucleotides level by inactivating guanylyl cyclases directly or indirectly. The reduced cyclic nucleotides level modulate specific phosphorylation status of cyclin-dependent kinase 1 (Cdk1) and triggers cyclin B1 degradation. These changes result in maturation promoting factor (MPF) destabilization that finally triggers meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in most of the mammalian species.


1. MA Sirard: Resumption of meiosis: mechanism involved in meiotic progression and its relation with developmental competency. Theriogenology 55, 1241-1254 (2001)
DOI: 10.1016/S0093-691X(01)00480-0

2. A Tripathi, KV Prem Kumar, SK Chaube: Meiotic cell cycle arrest in mammalian oocytes. J Cell Physiol 223, 592-600 (2010)
DOI: 10.1002/jcp.22108

3. M Tiwari, S Prasad, TG Shrivastav, SK Chaube: Calcium signaling during meiotic cell cycle regulation and apoptosis in mammalian oocytes. J Cell Physiol 232, 976-981 (2017)
DOI: 10.1002/jcp.25670

4. A Trounson, C Anderiesz, G Jones: Maturation of human oocytes in vitro and their developmental competence. Reproduction 121, 51-75 (2001)
DOI: 10.1530/rep.0.1210051

5. AN Pandey, A Tripathi, KV Premkumar, TG Shrivastav, SK Chaube: Reactive oxygen and nitrogen species during meiotic resumption from diplotene arrest in mammalian oocytes. J Cell Biochem 111, 521-528 (2010)
DOI: 10.1002/jcb.22736

6. SK Chaube, TG Shrivastav, S Prasad, M Tiwari, A Tripathi, AN Pandey, KV Premkumar: Clomiphene citrate induces ROS-mediated apoptosis in mammalian oocytes. Open J Apoptosis 3, 52-58 (2014)
DOI: 10.4236/ojapo.2014.33006

7. SK Chaube, TG Shrivastav, M Tiwari, S Prasad, A Tripathi, AK Pandey: Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals. SpringerPlus 3, 464 (1-7) (2014)

8. SK Chaube, S Prasad, M Tiwari: Abortive Spontaneous Egg Activation: A limiting factor for reproductive outcome in mammals. RRJZS 4, 1-2 (2016)

9. SK Chaube, S Prasad, M Tiwari, A Gupta: Rat: An interesting model to study oocyte meiosis in mammals. RRJZS 4, 25-27 (2017)

10. LM Mehlmann: Stops and starts in mammalian oocytes: Recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction 130, 791-799 (2005)
DOI: 10.1530/rep.1.00793

11. M Tiwari, S Prasad, A Tripathi, AN Pandey, I Ali, AK Singh, TG Shrivastav, SK Chaube: Apoptosis in mammalian oocytes: A review. Apoptosis 20, 1019-1025 (2015)
DOI: 10.1007/s10495-015-1136-y

12. M Tiwari, S Prasad, A Tripathi, AN Pandey, AK Singh, TG Shrivastav, SK Chaube: Involvement of reactive oxygen species in meiotic cell cycle regulation and apoptosis in mammalian oocytes. Reactive Oxygen Species 1, 110-116 (2016)
DOI: 10.20455/ros.2016.817

13. SK Chaube: Does cyclic adenosine 3&vprime;, 5&vprime; monophosphate act as a regulator for oocyte meiotic resumption in mammal? HPPI 25, 74-85 (2002)

14. RB Gilchrist: Recent insights into oocyte-follicle cell interactions provide opportunities for the development of new approaches to in vitro maturation. Reprod Fertil Dev 23, 23-31 (2011)
DOI: 10.1071/RD10225

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

16. M Tiwari, SK Chaube: Moderate increase of reactive oxygen species triggers meiotic resumption in rat follicular oocytes. J Obstet Gynaecol Res 42, 536-546 (2016)
DOI: 10.1111/jog.12938

17. A Gupta, M Tiwari, S Prasad, SK Chaube: Role of cyclic nucleotide phosphodiesterases during meiotic resumption from diplotene arrest in mammalian oocytes. J Cell Biochem 180, 446-452 (2017)
DOI: 10.1002/jcb.25748

18. DF Albertini: A cell for every season: The ovarian granulosa cell. J Assist Reprod Genet 28, 877-878 (2011)
DOI: 10.1007/s10815-011-9648-z
PMid:22020532 PMCid:PMC3220433

19. AN Pandey, SK Chaube: Reduction of nitric oxide level leads to spontaneous resumption of meiosis in diplotene-arrested rat oocytes cultured in vitro. Exp Biol Med (Maywood) 240, 15-25 (2015)
DOI: 10.1177/1535370214545024
PMid:25092827 PMCid:PMC4935180

20. S Prasad, M Tiwari, A Tripathi, AN Pandey, SK Chaube: Changes in signal molecules and maturation promoting factor levels associate with spontaneous resumption of meiosis in rat oocytes. Cell Biol Int 39, 759-769 (2015)
DOI: 10.1002/cbin.10444

21. T Chebotareva, J Taylor, JJ Mullins, I Wilmut: Rat eggs cannot wait: Spontaneous exit from meiotic metaphase-II arrest. Mol Reprod Dev 78, 795-807 (2011)
DOI: 10.1002/mrd.21385

22. S Prasad, M Tiwari, B Koch, SK Chaube: Morphological, cellular and molecular changes during postovulatory aging in mammals. J Biomed Sci 22:36 (2015)

23. S Prasad, B Koch, SK Chaube: Maturation promoting factor destabilization facilitates postovulatory aging-mediated abortive spontaneous egg activation in rat. Dev Growth Differ 58, 293-302 (2016)
DOI: 10.1111/dgd.12272

24. S Prasad, M Tiwari, AN Pandey, TG Shrivastav, SK Chaube: Impact of stress on oocyte quality and reproductive outcome. J Biomed Sci 23:36 (2016)

25. M Tiwari, A Tripathi, SK Chaube: Presence of encircling granulosa cells protects against oxidative stress-induced apoptosis in rat eggs cultured in vitro. Apoptosis 22, 98-107 (2017)
DOI: 10.1007/s10495-016-1324-4

26. KV Premkumar, SK Chaube: Nitric oxide signals postovulatory aging-induced abortive spontaneous egg activation in rats. Redox Rep 20, 184-192 (2015)
DOI: 10.1179/1351000215Y.0000000003

27. KV Premkumar, SK Chaube: Increased level of reactive oxygen species persuades postovulatory aging mediated spontaneous egg activation in rat eggs cultured in vitro. In vitro Cell Dev Biol Anim 52, 576-588 (2016)
DOI: 10.1007/s11626-016-0007-3

28. KV Premkumar, SK Chaube: An insufficient increase in cytosolic free calcium level results postovulatory aging-induced abortive spontaneous egg activation in rat. J Assist Reprod Genet 30, 117-123 (2013)
DOI: 10.1007/s10815-012-9908-6
PMid:23239129 PMCid:PMC3553342

29. KV Premkumar, SK Chaube: RyR channel-mediated increase of cytosolic free calcium level signals cyclin B1 degradation during abortive spontaneous egg activation in rat. In vitro Cell Dev Biol Anim 50, 640-647 (2014)
DOI: 10.1007/s11626-014-9749-y

30. J Sudiman, LJ Ritter, DK Feil, X Wang, K Chan, DG Mottershead, DM Robertson, JG Thompson, RB Gilchrist: Effects of differing oocyte-secreted factors during mouse in vitro maturation on subsequent embryo and fetal development. J Assist Reprod Genet 31, 295-306 (2014)
DOI: 10.1007/s10815-013-0152-5
PMid:24408183 PMCid:PMC3947075

31. Y Nakamura, Y Yamagata, N Sugino, H Takayama, H Kato: Nitric oxide inhibits oocyte meiotic maturation. Biol Reprod 67, 1588-1592 (2002)
DOI: 10.1095/biolreprod.102.005264

32. X Cui, J Zhang, P Ma, DE Myers, IG Goldberg, KJ Sittler, JJ Barb, PJ Munson, PA Cintrond, JP McCoy, S Wang, RL Danner: cGMP independent nitric oxide signaling and regulation of the cell cycle. BMC Genomics 6:151 (2005)

33. JG Thompson, HM Brown, KL Kind, DL Russell: The ovarian antral follicle: Living on the edge of hypoxia or not? Biol Reprod 92:153 (2015)

34. A Jablonka-Shariff, LM Olson: Hormonal regulation of nitric oxide synthases and their cell-specific expression during follicular development in the rat ovary. Endocrinology 138, 460-468 (1997)
DOI: 10.1210/en.138.1.460

35. PA Bush, NE Gonzalez, JM Griscavage, LJ Ignarro: Nitric oxide synthase from cerebellum catalyzes the formation of equimolar quantities of nitric oxide and citrulline from L-arginine. Biochem Biophys Res Commun 185, 960-966 (1992)
DOI: 10.1016/0006-291X(92)91720-B

36. RM Palmer, S Moncada: A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells. Biochem Biophys Res Commun 158, 348-352 (1989)
DOI: 10.1016/S0006-291X(89)80219-0

37. S Moncada, RM Palmer, EA Higgs: Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol Rev 43, 109-142 (1991)

38. S Nagase, K Takemura, A Ueda, A Hirayama, K Aoyagi, M Kondoh, A Koyama: A novel non enzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D- or L-arginine. Biochem Biophys Res Commun 233, 150-153 (1997)
DOI: 10.1006/bbrc.1997.6428

39. A El-Sehemy, LM Postovit , Y Fu: Nitric oxide signaling in human ovarian cancer: A potential therapeutic target. Nitric Oxide 54, 30-37 (2016)
DOI: 10.1016/j.niox.2016.02.002

40. F Aktan: iNOS-mediated nitric oxide production and its regulation. Life Sci 75, 639-653 (2004)
DOI: 10.1016/j.lfs.2003.10.042

41. K Sengoku, N Takuma, M Horikawa, K Tsuchiya, H Komori, D Sharifa, K Tamate, M Ishikawa: Requirement of nitric oxide for murine oocyte maturation, embryo development and trophoblast outgrowth in vitro. Mol Reprod Dev 58, 262-268 (2001)
DOI: 10.1002/1098-2795(200103)58:3<262::AID-MRD3>3.0.CO;2-8

42. Y Tao, Z Fu, M Zhang, G Xia, J Yang, H Xie: Immunohistochemical localization of inducible and endothelial nitric oxide synthase in porcine ovaries and effects of NO on antrum formation and oocyte meiotic maturation. Mol Cell Endocrinol 222, 93-103 (2004)
DOI: 10.1016/j.mce.2004.04.014

43. Y Tao, H Xie, H Hong, X Chen, J Jang, G Xia: Effects of nitric oxide synthase inhibitors on porcine oocyte meiotic maturation. Zygote 13, 1-9 (2005)
DOI: 10.1017/S0967199404002953

44. NM Orsi: Embryotoxicity of the nitric oxide donor sodium nitroprusside in preimplantation bovine embryos in vitro. Anim Reprod Sci 91, 225-236 (2006)
DOI: 10.1016/j.anireprosci.2005.04.008

45. PT Goud, AP Goud, MP Diamond, B Gonik, HM Abu-Soud: Nitric oxide extends the oocyte temporal window for optimal fertilization. Free Radic Biol Med 45, 453-459 (2008)
DOI: 10.1016/j.freeradbiomed.2008.04.035
PMid:18489913 PMCid:PMC3786211

46. PR Pires, NP Santos, PR Adona, MM Natori, KR Schwarz, TH Camara de, CL Leal: Endothelial and inducible nitric oxide synthases in oocytes of cattle. Anim Reprod Sci 116, 233-243 (2009)
DOI: 10.1016/j.anireprosci.2009.02.019

47. MH Amale, AZ Shahne, S Nasrollahi: Effects of nitric oxide synthase inhibition on goat oocyte meiotic maturation. Arch Tierz 25, 255-263 (2013)

48. G Basini, F Grasselli: Nitric oxide in follicle development and oocyte competence. Reproduction 150, R1-R9 (2015)

49. BJ Van Voorhis, K Moore, PJ Strijbos, S Nelson, SA Baylis, D Grzybicki, CP Weiner: Expression and localization of inducible and endothelial nitric oxide synthase in the rat ovary. Effects of gonadotropin stimulation in vivo. J Clin Invest 96, 2719-2726 (1995)
DOI: 10.1172/JCI118339
PMid:8675639 PMCid:PMC185979

50. U Zackrisson, M Mikuni, A Wallin, D Delbro, L Hedin, M Bra’nnstrom: Cell-specific localization of nitric oxide synthases (NOS) in the rat ovary during follicular development, ovulation and luteal formation. Hum Reprod 11, 2667-2673 (1996)
DOI: 10.1093/oxfordjournals.humrep.a019189

51. SL Klein, D Carnovale, AL Burnett, EE Wallach, HA Zacur, JK Crone, VL Dawson, RJ Nelson, TM Dawson: Impaired ovulation in mice with targeted deletion of the neuronal isoform of nitric oxide synthase. Mol Med 4, 658-664 (1998)

52. H Kim, C Moon, M Ahn, Y Lee, H Kim, S Kim, T Ha, Y Je, T Shin: Expression of nitric oxide synthase isoforms in the porcine ovary during follicular development. J Vet Sci 6, 97-101 (2005)

53. KS Viana, MC Caldas-Bussiere, SGC Matta, MR Faes, CSP de Carvalho, CR Quirino: Effect of sodium nitroprusside, a nitric oxide donor, on the in vitro maturation of bovine oocytes. Anim Reprod Sci 102, 217-227 (2007)
DOI: 10.1016/j.anireprosci.2006.11.004

54. E Chmelikova, M Sedmikova, J Peter, T Kott, V Lanska, L Tumova, H Tichovska, M Jeseta: Expression and localization of nitric oxide synthase isoforms during porcine oocyte growth and acquisition of meiotic competence. Czech J Anim Sci 54, 137-149 (2009)

55. K Takesue, S Tabata, F Sato, MA Hattori: Expression of nitric oxide synthas-3 in porcine oocytes obtained at different follicular development. J Reprod Dev 49, 135-140 (2003)
DOI: 10.1262/jrd.49.135

56. A Jablonka-Shariff, LM Olson: The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. Endocrinology 139, 2944-2954 (1998)
DOI: 10.1210/en.139.6.2944

57. A Jablonka-Shariff, S Ravi, AN Beltsos, LL Murphy, LM Olson: Abnormal estrous cyclicity after disruption of endothelial and inducible nitric oxide synthase in mice. Biol Reprod 61, 171–177 (1999)
DOI: 10.1095/biolreprod61.1.171

58. A Jablonka-Shariff, L Olson: Nitric oxide is essential for optimal meiotic maturation of murine cumulus-oocyte complexes in vitro. Mol Reprod Dev 55, 412-421 (2000)
DOI: 10.1002/(SICI)1098-2795(200004)55:4<412::AID-MRD9>3.0.CO;2-W

59. LJ Huo, C Liang, LZ Yu, ZS Zhong, Z Yang, HY Fan, DY Chen, QY Sun: Inducible nitric oxide synthase-derived nitric oxide regulates germinal vesicle breakdown and first polar body emission in the mouse oocyte. Reproduction 129, 403-409 (2005)
DOI: 10.1530/rep.1.0542

60. S Bu, G Xia, Y Tao, L Lei, B Zhou: Dual effects of nitric oxide on meiotic maturation of mouse cumulus cell-enclosed oocytes in vitro. Mol Cell Endocrinol 207, 21-30 (2003)
DOI: 10.1016/S0303-7207(03)00213-2

61. KR Schwarz, PR Pires, PR Adona, TH Camara de, CL Leal: Influence of nitric oxide during maturation on bovine oocyte meiosis and embryo development in vitro. Reprod Fertil Dev 20, 529-536 (2008)
DOI: 10.1071/RD07209

62. KR Schwarz, PR Pires, LG Mesquita, MR Chiaratti, CL Leal: Effect of nitric oxide on the cyclic guanosine monophosphate (cGMP) pathway during meiosis resumption in bovine oocytes. Theriogenology 81, 556-564 (2014)
DOI: 10.1016/j.theriogenology.2013.11.008

63. A Tripathi, S Khatun, AN Pandey, SK Mishra, R Chaube, TG Shrivastav, SK Chaube: Intracellular levels of hydrogen peroxide and nitric oxide in oocytes at various stages of meiotic cell cycle and apoptosis. Free Radic Res 43. 287-294 (2009)

64. S Saugandhika, D Kumar, MK Singh, R Shah, T Anand, MS Chauhan, RS Manik, SK Singla, P Palta: Effect of sodium nitroprusside, a nitric oxide donor, and aminoguanidine, a nitric oxide synthase inhibitor, on in vitro development of buffalo (Bubalus bubalis) embryos. Reprod Dom Anim 45, 931-933 (2010)

65. AP Goud, PT Goud, MP Diamond, HM Abu-Soud: Nitric oxide delays oocyte aging. Biochemistry 44, 11361-11368 (2005)
DOI: 10.1021/bi050711f

66. M Conti: Specificity of the cyclic adenosine 3&vprime;, 5&vprime;-monophosphate signal in granulosa cell function. Biol Reprod 67, 1653-1661 (2002)
DOI: 10.1095/biolreprod.102.004952

67. M Conti: Signaling networks in somatic cells and oocytes activated during ovulation. Ann Endocrinol (Paris) 71, 189-190 (2010)
DOI: 10.1016/j.ando.2010.02.010

68. S Madgwick, KT Jones: How eggs arrest at metaphase-II: MPF stabilization plus APC/C inhibition equals cytostatic factor. Cell Div 2, 4-11 (2007)
DOI: 10.1186/1747-1028-2-4
PMid:17257429 PMCid:PMC1794241

69. M Mrazek, J Jr Fulka Jr: Failure of oocyte maturation: possible mechanisms for oocyte maturation arrest. Hum Reprod 18, 2249-2252 (2003)
DOI: 10.1093/humrep/deg434

70. Y Zhang, Z Zhang, XY Xu, XS Li, M Yu, AM Yu, ZH Zong, BZ Yu: Protein kinase A modulates Cdc25B activity during meiotic resumption of mouse oocytes. Dev Dyn 237, 3777-3786 (2008)
DOI: 10.1002/dvdy.21799

71. M Zhang, H Ouyang, G Xia: The signal pathway of gonadotrophins induced mammalian oocyte meiotic resumption. Mol Hum Reprod 15, 399-409 (2009)
DOI: 10.1093/molehr/gap031

72. M Hattori, N Nishida, K Takesue, Y Kato, N Fujihara: FSH suppression of nitric oxide synthesis in porcine oocytes. J Mol Endocrinol 24, 65-73 (2000)
DOI: 10.1677/jme.0.0240065

73. Y Yamagata, Y Nakamura, N Sugino, A Harada, H Takayama, S Kashida, H Kato: Alterations in nitrate/nitrite and nitric oxide synthase in preovulatory follicles in gonadotropin-primed immature rat. Endocrinology 49, 219-226 (2002)
DOI: 10.1507/endocrj.49.219

74. S Sela-Abramovich, D Galiani, N Nevo, N Dekel: Inhibition of rat oocyte maturation and ovulation by nitric oxide: mechanism of action. Biol Reprod 78, 1111-1118 (2008)
DOI: 10.1095/biolreprod.107.065490

75. MA Hattori, K Takesue, Y Kato, N Fujihara: Expression of endothelial nitric oxide synthase in the porcine oocyte and its possible function. Mol Cell Biochem 219, 121-126 (2001)
DOI: 10.1023/A:1010830507846

76. LM Mitchell, CR Kennedy, M Geraldine, GM Hartshorne: Expression of nitric oxide synthase and effect of substrate manipulation of the nitric oxide pathway in mouse ovarian follicles. Hum Reprod 19, 30-40 (2004)
DOI: 10.1093/humrep/deh032

77. S Bilodeau-Goeseels: Effects of manipulating the nitric oxide/cyclic GMP pathway on bovine oocyte meiotic resumption in vitro. Theriogenology 68, 693-701 (2007)
DOI: 10.1016/j.theriogenology.2007.05.063

78. F Amidi, M Abbasi, M Akbari, E Sato, AR Dehpour, S Ejtemaei-Mehr, F Abolhassani: In vitro meiotic maturation of mouse oocytes: Role of nitric oxide. Acta Med Iran 45, 329-338 (2007)

79. M Abbasi, M Akbari, F Amidi, I Ragrdi Kashani, R Mahmoudi, A Sobhani, N Takzare, P Pasbhakush, M Barbarestani, F Abolhassani, E Sato: Nitric oxide acts through different signaling pathways in maturation of cumulus cell-enclosed mouse oocytes. DARU 17, 48-52 (2009)

80. P Ji-Hoon, L Bong-Koo, C Young-Ho, R Man-Hee, SK Kim: Effects of sodium nitroprusside and nitric oxide on in vitro maturation of canine oocytes. Reprod Dev Biol 35, 469-473 (2011)

81. SK Chaube: Role of meiotic maturation regulatory factors in the meiotic competence of mammalian oocytes. HPPI 24, 218-231 (2001)

82. A Vignini, A Turi, SR Giannubilo, D Pescosolido, P Scognamiglio, S Zanconi, C Silvi, L Mazzanti, AL Traquilli: Follicular fluid nitric oxide (NO) concentrations in stimulated cycles: The relationship to embryo grading. Arch Gynecol Obstet 277, 229-232 (2008)
DOI: 10.1007/s00404-007-0445-y

83. J Tornell, H Billig, T Hillensjo: Resumption of rat oocyte meiosis is paralleled by a decrease in guanosine 3,5-cyclic monophosphate (cGMP) and is inhibited by microinjection of cGMP. Acta Physiol Scand 139, 511-517 (1990)
DOI: 10.1111/j.1748-1716.1990.tb08953.x

84. S Wang, G Ning, X Chain, J Yang, H Ouyang, H Zhang, P Tai, X Mu, B Zhou, M Zhang: PDE5 modulates oocyte spontaneous maturation via cGMP cAMP but not cAMP-PKG signaling. Front Biosci 13, 7087-7095 (2008)
DOI: 10.2741/3212

85. LA Jaffe, RP Norris: Initiation of the meiotic prophase to metaphase transition in mammalian oocytes. Oogenesis. In: Verlhac M-H, Villenuve A (eds) Oogenesis: The universal process. New York: Wiley, 181-198 (2010)

86. SJ Han, M Conti: New pathways from PKA to Cdc2/cyclin B complex in oocytes wee1B as a potential PKA substrate. Cell cycle 5, 227-231 (2006)
DOI: 10.4161/cc.5.3.2395

87. JJ Eppig, MM Viveiros, C Marin-Bivens, Fuente R De La: Regulation of mammalian oocyte maturation. In: Leung PCK, Adashi EY (Eds.). The Ovary. Second ed. San Diego, California: Elsevier Academic Press 113-129 (2004)

88. G Liang, YQ Su, HY Fan, H Schatten, QY Sun: Mechanisms regulating oocyte meiotic maturation: Roles of mitogen-activated protein kinase. Mol Endocrinol 21, 2037-2055 (2007)
DOI: 10.1210/me.2006-0408

89. P Solc, RM Schultz, J Motlik: 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 16, 654-664 (2010)
DOI: 10.1093/molehr/gaq034
PMid:20453035 PMCid:PMC2930517

90. BC Duckworth, JS Weaver, JV Ruderman: G2 arrest in xenopus oocytes depends on phosphorylation of cdc25 by protein kinase A. Proc Natl Acad Sci USA 99, 16794-16799 (2002)
DOI: 10.1073/pnas.222661299
PMid:12477927 PMCid:PMC139223

91. AJ Lincoln, D Wickramasinghe, P Stein, RM Schultz, ME Palko, MP De Miguel, L Tessarollo, PJ Donovan: Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation. Nat Genet 30, 446-449 (2002)
DOI: 10.1038/ng856

92. JZ Kubiak, MA Ciemerych, A Hupalowska, M Sikora-Polaczek, Z Polanski: On the transition from the meiotic cell cycle during early mouse development. Int J Dev Biol 52, 201-217 (2008)
DOI: 10.1387/ijdb.072337jk

93. F Chesnel, F Bazile, A Pascal, JZ Kubiak: Cyclin B dissociation from CDK1 precedes its degradation upon MPF inactivation in mitotic extracts of Xenopus laevis embryos. Cell Cycle 5, 1687-1698 (2006)
DOI: 10.4161/cc.5.15.3123

94. JS Oh, A Susor, M Conti: Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse oocytes. Science 332, 462-465 (2011)
DOI: 10.1126/science.1199211

95. JS Oh, A Susor, K Schindler, RM Schultz, M Conti: Cdc25A activity is required for the metaphase II arrest in mouse oocytes. J Cell Sci 126, 1081-1085 (2013)
DOI: 10.1242/jcs.115592

96. YL Miao, K Kikuchi, QY Sun, H Schatten: Oocyte aging: Cellular and molecular changes, developmental potential and reversal possibility. Hum Reprod 5, 573-585 (2009)
DOI: 10.1093/humupd/dmp014

97. S Prasad, SK Chaube: S-nitroso-N-acetyl penicillamine inhibits spontaneous exit from metaphase-II arrest in rat eggs cultured in vitro. Biomed Pharmacother 84, 680-686 (2016)
DOI: 10.1016/j.biopha.2016.09.059

98. HH Schmidt, U Walter: NO at work. Cell 78, 919- 925 (1994)
DOI: 10.1016/0092-8674(94)90267-4

99. SR Vincent: Nitric oxide: a radical neurotransmitter in the central nervous system. Prog Neurobiol 42, 129-160 (1994)
DOI: 10.1016/0301-0082(94)90023-X

100. C Tatone, GD Emidio, R Barbaro, M Vento, R Ciriminna, PG Artini: Effects of reproductive aging and postovulatory aging on the maintenance of biological competence after oocyte vitrification: insights from the mouse model. Theriogenology 76, 864-873 (2011)
DOI: 10.1016/j.theriogenology.2011.04.017

Abbreviations: AC, adenylyl cyclases; AG, Aminoguanidine; ART, assisted reproductive outcome; Ca2+, calcium; cAMP, adenosine 3&vprime;,5&vprime;-cyclic monophosphate; Cdk1, cyclin-dependent kinase 1; cGMP, 3&vprime;, 5&vprime;-cyclic monophosphate; COCs, cumulus-oocyte complexes; eNOS, endothelial nitric oxide synthase; GC, guanylyl cyclases; GV, germinal vesicle; GVBD, germinal vesicle breakdown; H2O2, hydrogen peroxide, hCG, human chorionic gonadotropin; iNOS, inducible nitric oxide synthase; LH, luteinizing hormone; MAPK, mitogen-activated protein kinase; M-I, Metaphase-I; M-II, Metaphase-II; M-III, Metaphase-III; MPF, maturation promoting factor; nNOS, neuronal nitric oxide synthase; NO, nitric oxide; NOS, nitric oxide synthases; PB-I, first polar body; PB-II, second polar body; PDE3A, phosphodiesterase 3A; PKA, protein kinase A; PMSG, pregnant mare’s serum gonadotropin; RNS, reactive nitrogen species; ROS, reactive oxygen species; SNAP, S-nitroso, N-acetyl penicillamine; SNP, sodium nitroprusside.

Key Words: Nitric oxide, Oocyte physiology, Cyclic nucleotides, MPF, Meiotic cell cycle, Review

Send correspondence to: Shail K. Chaube, Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi-221005, India, Tel: 91-542-26702516, Fax: 91-542-2368174, E-mail: shailchaube@bhu.ac.in