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Reproductive Biology and Endocrinology

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Open Access 01-12-2015 | Research

Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes

Authors: Milan Blaha, Lucie Nemcova, Radek Prochazka

Published in: Reproductive Biology and Endocrinology | Issue 1/2015

Abstract

Background

Recent results indicate a key role for cyclic guanosine monophosphate (cGMP) in the regulation of oocyte meiotic arrest in preovulatory mammalian follicles. The aim of our study was to determine whether the resumption of oocyte meiosis and expansion of cumulus cells in isolated pig cumulus-oocyte complexes (COCs) can be blocked by a high intracellular concentration of cGMP, and whether this effect is mediated by a cGMP-dependent inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1).

Methods

The COCs were isolated from ovaries of slaughtered gilts and cultured in vitro in M199 supplemented with 5% fetal calf serum. The expression levels of the C-type natriuretic peptide (CNP) precursor (NPPC) and its receptor (NPR2) mRNAs during the culture of COCs were determined by real-time RT-PCR. To control the intracellular concentration of cGMP in the COCs, the culture medium was further supplemented with CNP or various concentrations of synthetic cGMP analogues; the concentration of cGMP in COCs was then assessed by ELISA. The effect of the drugs on oocyte maturation was assessed after 24 and 44 h of culture by determining nuclear maturation. The expansion of cumulus cells was assessed by light microscopy and the expression of cumulus expansion-related genes by real-time RT-PCR. A possible effect of cGMP on FSH-induced activation of MAPK3/1 was assessed by immunoblotting the COC proteins with phospho-specific and total anti-Erk1/2 antibodies.

Results

The COCs expressed NPPC and NPR2, the key components of cGMP synthesis, and produced a large amount of cGMP upon stimulation with exogenous CNP, which lead to a significant (P < 0.05) delay in oocyte meiotic resumption. The COCs also responded to cGMP analogues by inhibiting the resumption of oocyte meiosis. The inhibitory effect of cGMP on meiotic resumption was reversed by stimulating the COCs with FSH. However, high concentration of intracellular cGMP was not able to suppress FSH-induced activation of MAPK3/1 in cumulus cells, cumulus expansion and expression of expansion-related genes (P > 0.05).

Conclusions

The findings of this study indicate that high cGMP concentrations inhibit the maturation of pig oocytes in vitro but the inhibitory mechanism does not involve the suppression of MAPK3/1 activation in cumulus cells.

Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, Pendola FL, Knowles BB, Eppig JJ, Jaffe LA: The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science 2004, 306:1947–50. 10.1126/science.1103974PubMedCrossRef

Yang CR, Wei Y, Qi ST, Chen L, Zhang QH, Ma JY, Luo YB, Wang YP, Hou Y, Schatten H, et al.: The G protein coupled receptor 3 is involved in cAMP and cGMP signaling and maintenance of meiotic arrest in porcine oocytes. PLoS One 2012, 7:e38807. 10.1371/journal.pone.0038807PubMedCentralPubMedCrossRef

Tsafriri A, Chun SY, Zhang R, Hsueh AJ, Conti M: Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol 1996, 178:393–402. 10.1006/dbio.1996.0226PubMedCrossRef

Wiersma A, Hirsch B, Tsafriri A, Hanssen RG, Van de Kant M, Kloosterboer HJ, Conti M, Hsueh AJ: Phosphodiesterase 3 inhibitors suppress oocyte maturation and consequent pregnancy without affecting ovulation and cyclicity in rodents. J Clin Invest 1998, 102:532–7. 10.1172/JCI2566PubMedCentralPubMedCrossRef

Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA: Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development 2009, 136:1869–78. 10.1242/dev.035238PubMedCentralPubMedCrossRef

Vaccari S, Weeks JL, Hsieh M, Menniti FS, Conti M: Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod 2009, 81:595–604. 10.1095/biolreprod.109.077768PubMedCentralPubMedCrossRef

Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ: Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science 2010, 330:366–9. 10.1126/science.1193573PubMedCentralPubMedCrossRef

Robinson JW, Zhang M, Shuhaibar LC, Norris RP, Geerts A, Wunder F, Eppig JJ, Potter LR, Jaffe LA: Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes. Dev Biol 2012, 366:308–16. 10.1016/j.ydbio.2012.04.019PubMedCentralPubMedCrossRef

Norris RP, Freudzon M, Mehlmann LM, Cowan AE, Simon AM, Paul DL, Lampe PD, Jaffe LA: 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, 135:3229–38. 10.1242/dev.025494PubMedCentralPubMedCrossRef

10.

Norris RP, Freudzon M, Nikolaev VO, Jaffe LA: 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, 140:655–62. 10.1530/REP-10-0288PubMedCentralPubMedCrossRef

11.

Hsieh M, Thao K, Conti M: Genetic dissection of epidermal growth factor receptor signaling during luteinizing hormone-induced oocyte maturation. PLoS One 2011, 6:e21574. 10.1371/journal.pone.0021574PubMedCentralPubMedCrossRef

12.

Park JY, Su YQ, Ariga M, Law E, Jin SL, Conti M: EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science 2004, 303:682–4. 10.1126/science.1092463PubMedCrossRef

13.

Prochazka R, Petlach M, Nagyova E, Nemcova L: Effect of epidermal growth factor-like peptides on pig cumulus cell expansion, oocyte maturation, and acquisition of developmental competence in vitro: comparison with gonadotropins. Reproduction 2011, 141:425–35. 10.1530/REP-10-0418PubMedCrossRef

14.

Zamah AM, Hsieh M, Chen J, Vigne JL, Rosen MP, Cedars MI, Conti M: Human oocyte maturation is dependent on LH-stimulated accumulation of the epidermal growth factor-like growth factor, amphiregulin. Hum Reprod 2010, 25:2569–78. 10.1093/humrep/deq212PubMedCentralPubMedCrossRef

15.

Kawamura K, Cheng Y, Kawamura N, Takae S, Okada A, Kawagoe Y, Mulders S, Terada Y, Hsueh AJ: 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, 26:3094–101. 10.1093/humrep/der282PubMedCrossRef

16.

Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ: Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology 2011, 152:4377–85. 10.1210/en.2011-1118PubMedCentralPubMedCrossRef

17.

Sasseville M, Côté N, Gagnon MC, Richard FJ: Up-regulation of 3′5′-cyclic guanosine monophosphate-specific phosphodiesterase in the porcine cumulus-oocyte complex affects steroidogenesis during in vitro maturation. Endocrinology 2008, 149:5568–76. 10.1210/en.2008-0547PubMedCrossRef

18.

Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, Dey SK: Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 1997, 91:197–208. 10.1016/S0092-8674(00)80402-XPubMedCrossRef

19.

Fülöp C, Szántó S, Mukhopadhyay D, Bárdos T, Kamath RV, Rugg MS, Day AJ, Salustri A, Hascall VC, Glant TT, et al.: Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development 2003, 130:2253–61. 10.1242/dev.00422PubMedCrossRef

20.

Richards JS: Ovulation: new factors that prepare the oocyte for fertilization. Mol Cell Endocrinol 2005, 234:75–9. 10.1016/j.mce.2005.01.004PubMedCrossRef

21.

Shimada M, Hernandez-Gonzalez I, Gonzalez-Robayna I, Richards JS: Paracrine and autocrine regulation of epidermal growth factor-like factors in cumulus oocyte complexes and granulosa cells: key roles for prostaglandin synthase 2 and progesterone receptor. Mol Endocrinol 2006, 20:1352–65. 10.1210/me.2005-0504PubMedCrossRef

22.

Fan HY, Liu Z, Shimada M, Sterneck E, Johnson PF, Hedrick SM, Richards JS: MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science 2009, 324:938–41. 10.1126/science.1171396PubMedCentralPubMedCrossRef

23.

Yamashita Y, Hishinuma M, Shimada M: Activation of PKA, p38 MAPK and ERK1/2 by gonadotropins in cumulus cells is critical for induction of EGF-like factor and TACE/ADAM17 gene expression during in vitro maturation of porcine COCs. J Ovarian Res 2009, 2:20. 10.1186/1757-2215-2-20PubMedCentralPubMedCrossRef

24.

Prochazka R, Blaha M, Nemcova L: Signaling pathways regulating FSH- and amphiregulin-induced meiotic resumption and cumulus cell expansion in the pig. Reproduction 2012, 144:535–46. 10.1530/REP-12-0191PubMedCrossRef

25.

Su YQ, Wigglesworth K, Pendola FL, O’Brien MJ, Eppig JJ: Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse. Endocrinology 2002, 143:2221–32. 10.1210/endo.143.6.8845PubMedCrossRef

26.

Sela-Abramovich S, Galiani D, Nevo N, Dekel N: Inhibition of rat oocyte maturation and ovulation by nitric oxide: mechanism of action. Biol Reprod 2008, 78:1111–8. 10.1095/biolreprod.107.065490PubMedCrossRef

27.

Zhang M, Tao Y, Zhou B, Xie H, Wang F, Lei L, Huo L, Sun Q, Xia G: Atrial natriuretic peptide inhibits the actions of FSH and forskolin in meiotic maturation of pig oocytes via different signaling pathways. J Mol Endocrinol 2005, 34:459–72. 10.1677/jme.1.01673PubMedCrossRef

28.

Santiquet N, Papillon-Dion E, Djender N, Guillemette C, Richard FJ: New elements in the C-type natriuretic peptide signaling pathway inhibiting swine in vitro oocyte meiotic resumption. Biol Reprod 2014, 91:16. 10.1095/biolreprod.113.114132PubMedCrossRef

29.

Hiradate Y, Hoshino Y, Tanemura K, Sato E: C-type natriuretic peptide inhibits porcine oocyte meiotic resumption. Zygote 2013, 18:1–6. doi:10.1017/S0967199412000615

30.

Vanderhyden BC, Caron PJ, Buccione R, Eppig JJ: Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation. Dev Biol 1990, 140:307–17. 10.1016/0012-1606(90)90081-SPubMedCrossRef

31.

Tsuji T, Kiyosu C, Akiyama K, Kunieda T: CNP/NPR2 signaling maintains oocyte meiotic arrest in early antral follicles and is suppressed by EGFR-mediated signaling in preovulatory follicles. Mol Reprod Dev 2012, 79:795–802. 10.1002/mrd.22114PubMedCrossRef

32.

Motlik J, Fulka J: Breakdown of the germinal vesicle in pig oocytes in vivo and in vitro. J Exp Zool 1976, 198:155–62. 10.1002/jez.1401980205PubMedCrossRef

33.

Egbert JR, Shuhaibar LC, Edmund AB, Van Helden DA, Robinson JW, Uliasz TF, Baena V, Geerts A, Wunder F, Potter LR, et al.: Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes. Development 2014, 141:3594–604. 10.1242/dev.112219PubMedCrossRef

34.

Sela-Abramovich S, Chorev E, Galiani D, Dekel N: Mitogen-activated protein kinase mediates luteinizing hormone-induced breakdown of communication and oocyte maturation in rat ovarian follicles. Endocrinology 2005, 146:1236–44. 10.1210/en.2004-1006PubMedCrossRef

35.

Sasseville M, Gagnon MC, Guillemette C, Sullivan R, Gilchrist RB, Richard FJ: Regulation of gap junctions in porcine cumulus-oocyte complexes: contributions of granulosa cell contact, gonadotropins, and lipid rafts. Mol Endocrinol 2009, 23:700–10. 10.1210/me.2008-0320PubMedCrossRef

36.

Santiquet NW, Develle Y, Laroche A, Robert C, Richard FJ: Regulation of gap-junctional communication between cumulus cells during in vitro maturation in swine, a gap-FRAP study. Biol Reprod 2012, 87:46. 10.1095/biolreprod.112.099754PubMedCrossRef

37.

Wigglesworth K, Lee KB, 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. Proc Natl Acad Sci U S A 2013, 110:E3723–9. 10.1073/pnas.1314829110PubMedCentralPubMedCrossRef

38.

Abbey-Hosch SE, Smirnov D, Potter LR: Differential regulation of NPR-B/GC-B by protein kinase c and calcium. Biochem Pharmacol 2005, 70:686–94. 10.1016/j.bcp.2005.04.034PubMedCrossRef

39.

Zhang M, Tao Y, Xia G, Xie H, Hong H, Wang F, Lei L: Atrial natriuretic peptide negatively regulates follicle-stimulating hormone-induced porcine oocyte maturation and cumulus expansion via cGMP-dependent protein kinase pathway. Theriogenology 2005, 64:902–16. 10.1016/j.theriogenology.2004.12.012PubMedCrossRef

40.

Downs SM: Hypoxanthine regulation of oocyte maturation in the mouse: insights using hypoxanthine phosphoribosyltransferase-deficient animals. Biol Reprod 1997, 57:54–62. 10.1095/biolreprod57.1.54PubMedCrossRef

41.

Downs SM, Chen J: EGF-like peptides mediate FSH-induced maturation of cumulus cell-enclosed mouse oocytes. Mol Reprod Dev 2008, 75:105–14. 10.1002/mrd.20781PubMedCrossRef

42.

Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB: Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod 2010, 25:2999–3011. 10.1093/humrep/deq246PubMedCrossRef

43.

Lu Z, Xia G, Zhang J: Protein kinase C, rather than protein kinase A is involved in follicle-stimulating hormone-mediated meiotic resumption of mouse cumulus cell-enclosed oocytes in hypoxanthine-supplemented medium. Mol Cell Endocrinol 2001, 182:225–32. 10.1016/S0303-7207(01)00564-0PubMedCrossRef

44.

Fan HY, Huo LJ, Chen DY, Schatten H, Sun QY: Protein kinase C and mitogen-activated protein kinase cascade in mouse cumulus cells: cross talk and effect on meiotic resumption of oocyte. Biol Reprod 2004, 70:1178–87.PubMedCrossRef

45.

Hanna CB, Yao S, Wu X, Jensen JT: Identification of phosphodiesterase 9A as a cyclic guanosine monophosphate-specific phosphodiesterase in germinal vesicle oocytes: a proposed role in the resumption of meiosis. Fertil Steril 2012, 98:487–495.e1. 10.1016/j.fertnstert.2012.05.015PubMedCentralPubMedCrossRef

46.

Raines KW, Cao GL, Porsuphatana S, Tsai P, Rosen GM, Shapiro P: Nitric oxide inhibition of ERK1/2 activity in cells expressing neuronal nitric-oxide synthase. J Biol Chem 2004, 279:3933–40.PubMedCrossRef

47.

Murillo-Carretero M, Torroglosa A, Castro C, Villalobo A, Estrada C: S-Nitrosylation of the epidermal growth factor receptor: a regulatory mechanism of receptor tyrosine kinase activity. Free Radic Biol Med 2009, 46:471–9. 10.1016/j.freeradbiomed.2008.10.048PubMedCrossRef

48.

Ibiza S, Pérez-Rodríguez A, Ortega A, Martínez-Ruiz A, Barreiro O, García-Domínguez CA, Víctor VM, Esplugues JV, Rojas JM, Sánchez-Madrid F, et al.: Endothelial nitric oxide synthase regulates N-Ras activation on the Golgi complex of antigen-stimulated T cells. Proc Natl Acad Sci U S A 2008, 105:10507–12. 10.1073/pnas.0711062105PubMedCentralPubMedCrossRef

49.

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

50.

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

51.

Huo LJ, Liang CG, Yu LZ, Zhong ZS, Yang ZM, Fan HY, Chen DY, Sun QY: Inducible nitric oxide synthase-derived nitric oxide regulates germinal vesicle breakdown and first polar body emission in the mouse oocyte. Reproduction 2005, 129:403–9. 10.1530/rep.1.0542PubMedCrossRef

52.

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

53.

Petr J, Rajmon R, Chmelíková E, Tománek M, Lánská V, Pribánová M, Jílek F: Nitric-oxide-dependent activation of pig oocytes: the role of the cGMP-signaling pathway. Zygote 2006, 14:9–16. 10.1017/S0967199406003546PubMedCrossRef

Title: Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes
Authors: Milan Blaha
Lucie Nemcova
Radek Prochazka
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Reproductive Biology and Endocrinology / Issue 1/2015
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/1477-7827-13-1

ACC 2024 Congress

Springer Medicine

Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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