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

Reproductive Biology and Endocrinology

Radek Prochazka¹  Lucie Nemcova¹  Milan Blaha¹ 

[1] Laboratory of Developmental Biology, Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Rumburska 89, 277 21 Libechov, Czech Republic

关键词: MAPK3/1;    Expansion-related genes;    Meiotic resumption;    cGMP;    Oocyte;    Pig;   

Others  :  1131990
DOI  :  10.1186/1477-7827-13-1

 received in 2014-09-30, accepted in 2014-12-24,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Blaha et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]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.
• [2]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.
• [3]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.
• [4]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.
• [5]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.
• [6]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.
• [7]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.
• [8]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.
• [9]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]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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [20]Richards JS: Ovulation: new factors that prepare the oocyte for fertilization. Mol Cell Endocrinol 2005, 234:75-9.
• [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.
• [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.
• [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. BioMed Central Full Text
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [40]Downs SM: Hypoxanthine regulation of oocyte maturation in the mouse: insights using hypoxanthine phosphoribosyltransferase-deficient animals. Biol Reprod 1997, 57:54-62.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.
• [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.