NGF及其受体对卵泡发育调控的分子机制研究
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摘要
TrkA是神经营养因子(NGF)高亲和力的受体,而NGF是神经营养因子家族中的一员,TrkA被认为在卵巢卵泡发育过程成起重要作用,例如其参与原始卵泡的装配,也能促进早期卵泡的发育,还能诱导次级卵泡的分化,还能够促进卵母细胞的排出。然后,关于TrkA在卵丘卵母细胞复合物(COCs)扩展过程中所起的作用还不清楚。在本研究中,我们发现TrkA在大的有腔卵泡中表达丰富,所以TrkA可能在卵泡发育的后期发挥作用,其中就包括COCs的扩展。在卵丘颗粒细胞中沉默TrkA会抑制表皮生长因子(EGF)诱导的COCs的扩展,而且还降低了卵母细胞排出的比率。所以TrkA参与EGF诱导的卵丘细胞的扩展是很明确的。‘TrkA在COCs扩展过程中所起的作用不是通过EGF的下游分子ERK1/2或SMAD的磷酸化来实现的,也不是通过上调COCs扩展相关基因,例如前列腺素内过氧化物合酶2(Ptgs2),透明质酸合成酶2(Has2),肿瘤坏死因子诱导蛋白6(Tnfaipd),以及pentraxin3(Ptx3)来实现的。因此在这个过程中可能存在一个新的COCs扩展相关基因。然而,用K252a对TrkA进行药物阻断,抑制其信号转导活性,可以导致卵丘颗粒细胞内白细胞介素6(IL-6)的mRNA表达和蛋白分泌水平的下降,而IL-6是通过我们对COCs进行K252a预处理,然后进行mRNA微阵列分析而筛选出来的。此外,IL-6还可以恢复K252a对EGF诱导的卵丘颗粒细胞扩展的抑制效应,也恢复了K252a对卵母细胞排出的抑制效应。而且,COCs扩展相关基因和IL-6一样,在卵丘颗粒细胞中还是炎症相关基因。因此,IL-6可能作为一个新的潜在的卵丘颗粒细胞扩展相关基因,也可能涉及到TrkA信号通路和EGF信号通路在影响COCs扩展方面的交汇。在本研究中,我们对TrkA在EGF诱导的卵丘颗粒细胞扩展过程中的作用提供了一个机制方面的见解。理解TrkA和EGF影响卵丘颗粒细胞扩展潜在性的交叉点,有助于我们发现一些排卵相关疾病的新的治疗靶点。
TrkA, the high-affinity receptor of nerve growth factor (NGF), one of NTs family, is known to play key roles in ovarian follicular development, such as on assembling primordial follicles, promoting the early stages of follicular development, inducing the initial biochemical differentiation of secondary follicles into gonadotropin-responsive structures and facilitating ovulation. However, little is known about the roles of TrkA in cumulus oocyte complex (COCs) expansion.In this study, we found that TrkA was abundant in large antral follicles, so TrkA may play a role in the late stage of follicular development, such as cumulus expansion. Knockdown of TrkA in cumulus cells attenuated epidermal growth factor (EGF)-induced COCs expansion and further decreased the ovulation rate. So it is clear that TrkA participate in EGF-induced cumulus expansion. The effect of TrkA on COCs expansion was not mediated through downstream EGF effectors, phosphorylation of ERK1/2or SMAD, or through up-regulation of COCs expansion-related transcripts such as prostaglandin-endoperoxide synthase2(Ptgs2), hyaluronan synthase2(Has2), TNF-induced protein6(Tnfaip6) or pentraxin3(Ptx3). So there may be a new COCs expansion-related transcripts during this process. However, pharmacological blockade of TrkA transducing activity (K252a) in COCs decreased them RNA expression and protein secretion of interleukin-6(IL-6) in cumulus, identified from mRNA microarray of K252a-treated COCs. In addition, IL-6rescued the inhibitory effect of K252a on EGF-induced cumulus expansion, and on ovlation ratio. Furthermore, COCs expansion-related transcripts, as well as IL-6, also serve as inflammation-related genes in cumulus cells. Therefore, IL-6may act as a new potential cumulus expansion-related transcript, which may be involved in the integration of TrkA and EGF signaling in affecting COCs expansion. Here, we provide mechanistic insights into the roles of TrkA in EGF-induced cumulus expansion. Understanding potential cross-points between TrkA and EGF affecting cumulus expansion will help in the discovery of new therapeutic targets in ovulation-related diseases.
引文
Abir, R., Fisch, B., Jin, S., Barnnet, M., Ben-Haroush, A., Felz, C., Kessler-Icekson, G., Feldberg, D., Nitke, S., Ao, A.,2005. Presence of NGF and its receptors in ovaries from human fetuses and adults. Molecular human reproduction 11,229-236.
    Anderson, R.A., Robinson, L.L., Brooks, J., Spears, N.,2002. Neurotropins and their receptors are expressed in the human fetal ovary. The Journal of clinical endocrinology and metabolism 87, 890-897.
    Anesetti, G., Lombide, P., D'Albora, H., Ojeda, S.R.,2001. Intrinsic neurons in the human ovary. Cell and tissue research 306,231-237.
    Aravindakshan, J., Chen, X.L., Sairam, M.R.,2006. Age-dependent bimodal GDNF regulation during ovarian tumorigenesis in follitropin receptor mutant mice. Biochemical and biophysical research communications 351,507-513.
    Armstrong, D.G., Baxter, G., Gutierrez, C.G., Hogg, C.O., Glazyrin, A.L., Campbell, B.K., Bramley, T.A., Webb, R.,1998. Insulin-like growth factor binding protein -2 and -4 messenger ribonucleic acid expression in bovine ovarian follicles:effect of gonadotropins and developmental status. Endocrinology 139,2146-2154.
    Au, C.W., Siu, M.K., Liao, X., Wong, E.S., Ngan, H.Y., Tam, K.F., Chan, D.C., Chan, Q.K., Cheung, A.N.,2009. Tyrosine kinase B receptor and BDNF expression in ovarian cancers-Effect on cell migration, angiogenesis and clinical outcome. Cancer letters 281,151-161.
    Bagavandoss, P.,1998. Differential distribution of gelatinases and tissue inhibitor of metalloproteinase-1 in the rat ovary. The Journal of endocrinology 158,221-228.
    Bany, B.M., Schultz, G.A.,2001. Tissue inhibitor of matrix metalloproteinase-3 expression in the mouse uterus during implantation and artificially induced decidualization. Molecular reproduction and development 59,159-167.
    Barboni, B., Mattioli, M., Gioia, L., Turriani, M., Capacchietti, G., Berardinelli, P., Bernabo, N., 2002. Preovulatory rise of NGF in ovine follicular fluid:possible involvement in the control of oocyte maturation. Microscopy research and technique 59,516-521.
    Begliuomini, S., Casarosa, E., Pluchino, N., Lenzi, E., Centofanti, M., Freschi, L., Pieri, M., Genazzani, A.D., Luisi, S., Genazzani, A.R.,2007. Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Human reproduction 22,995-1002.
    Ben-Ami, I., Freimann, S., Armon, L., Dantes, A., Strassburger, D., Friedler, S., Raziel, A., Seger, R., Ron-El, R., Amsterdam, A.,2006. PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells:new insights into the coordination between PGE2 and LH in ovulation. Molecular human reproduction 12,593-599.
    Birren, S.J., Verdi, J.M., Anderson, D.J.,1992. Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells. Science 257,395-397.
    Boyer, A., Goff, A.K., Boerboom, D.,2010. WNT signaling in ovarian follicle biology and tumorigenesis. Trends in endocrinology and metabolism:TEM 21,25-32.
    Brannstrom, M., Woessner, J.F., Jr., Koos, R.D., Sear, C.H., LeMaire, W.J.,1988. Inhibitors of mammalian tissue collagenase and metalloproteinases suppress ovulation in the perfused rat ovary. Endocrinology 122,1715-1721.
    Brenner, C.A., Adler, R.R., Rappolee, D.A., Pedersen, R.A., Werb, Z.,1989. Genes for extracellular-matrix-degrading metalloproteinases and their inhibitor, TIMP, are expressed during early mammalian development. Genes & development 3,848-859.
    Buccione, R., Vanderhyden, B.C., Caron, P.J., Eppig, J.J.,1990. FSH-induced expansion^of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Developmental biology 138,16-25.
    Buratini, J., Jr., Teixeira, A.B., Costa, I.B., Glapinski, V.F., Pinto, M.G., Giometti, I.C., Barros, C.M., Cao, M., Nicola, E.S., Price, C.A.,2005. Expression of fibroblast growth factor-8 and regulation of cognate receptors, fibroblast growth factor receptor-3c and -4, in bovine antral follicles. Reproduction 130,343-350.
    Buyuk, E., Seifer, D.B.,2008. Follicular-fluid neurotrophin levels in women undergoing assisted reproductive technology for different etiologies of infertility. Fertility and sterility 90,1611-1615.
    Campos, X., Munoz, Y, Selman, A., Yazigi, R., Moyano, L., Weinstein-Oppenheimer, C., Lara, H.E., Romero, C.,2007. Nerve growth factor and its high-affinity receptor trkA participate in the control of vascular endothelial growth factor expression in epithelial ovarian cancer. Gynecologic oncology 104,168-175.
    Carletti, M.Z., Fiedler, S.D., Christenson, L.K.,2010. MicroRNA 21 blocks apoptosis in mouse periovulatory granulosa cells. Biology of reproduction 83,286-295.
    Cauffman, G., Van de Velde, H., Liebaers, I., Van Steirteghem, A.,2005. DAZL expression in human oocytes, preimplantation embryos and embryonic stem cells. Molecular human reproduction 11,405-411.
    Chaves, R.N., Alves, A.M., Lima, L.F., Matos, H.M., Rodrigues, A.P., Figueiredo, J.R.,2012. Role of nerve growth factor (NGF) and its receptors in folliculogenesis. Zygote,1-11.
    Chen, X., Zhou, B., Yan, J., Xu, B., Tai, P., Li, J., Peng, S., Zhang, M., Xia, G.,2008. Epidermal growth factor receptor activation by protein kinase C is necessary for FSH-induced meiotic resumption in porcine cumulus-oocyte complexes. The Journal of endocrinology 197,409-419.
    Choi, Y., Rajkovic, A.,2006. Genetics of early mammalian folliculogenesis. Cellular and molecular life sciences:CMLS 63,579-590.
    Copi, A., Jungling, K., Gottmann, K.,2005. Activity-and BDNF-induced plasticity of miniature synaptic currents in ES cell-derived neurons integrated in a neocortical network. Journal of neurophysiology 94,4538-4543.
    Cubeddu, A., Bucci, F., Giannini, A., Russo, M., Daino, D., Russo, N., Merlini, S., Pluchino, N., Valentino, V., Casarosa, E., Luisi, S., Genazzani, A.R.,2011. Brain-derived neurotrophic factor plasma variation during the different phases of the menstrual cycle in women with premenstrual syndrome. Psychoneuroendocrinology 36,523-530.
    Curry, T.E., Jr., Mann, J.S., Huang, M.H., Keeble, S.C.,1992. Gelatinase and proteoglycanase activity during the periovulatory period in the rat. Biology of reproduction 46,256-264.
    Curry, T.E., Jr., Osteen, K.G.,2001. Cyclic changes in the matrix metalloproteinase system in the ovary and uterus. Biology of reproduction 64,1285-1296.
    Curry, T.E., Jr., Osteen, K.G.,2003. The matrix metalloproteinase system:changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocrine reviews 24,428-465.
    Curry, T.E., Jr., Song, L., Wheeler, S.E.,2001. Cellular localization of gelatinases and tissue inhibitors of metalloproteinases during follicular growth, ovulation, and early luteal formation in the rat. Biology of reproduction 65,855-865.
    Davies, A.M.,1997. Neurotrophins:the yin and yang of nerve growth factor. Current biology:CB 7, R38-40.
    Davies, A.M.,2000. Neurotrophins:neurotrophic modulation of neurite growth. Current biology: CB 10,R198-200.
    Davies, A.M., Wright, E.M.,1995. Neurotrophic factors. Neurotrophin autocrine loops. Current biology:CB 5,723-726.
    Davis, B.J., Lennard, D.E., Lee, C.A., Tiano, H.F., Morham, S.G., Wetsel, W.C., Langenbach, R., 1999. Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-lbeta. Endocrinology 140,2685-2695.
    Dechant, G., Neumann, H.,2002. Neurotrophins. Advances in experimental medicine and biology 513,303-334.
    Dell'Aquila, M.E., Caillaud, M., Maritato, F., Martoriati, A., Gerard, N., Aiudi, G., Minoia, P., Goudet, G.,2004. Cumulus expansion, nuclear maturation and connexin 43, cyclooxygenase- 2 and FSH receptor mRNA expression in equine cumulus-oocyte complexes cultured in vitro in the presence of FSH and precursors for hyaluronic acid synthesis. Reproductive biology and endocrinology:RB&E 2,44.
    Despres, G., Romand, R.,1994. Neurotrophins and the development of cochlear innervation. Life sciences 54,1291-1297.
    Devine, P.J., Perreault, S.D., Luderer, U.,2012. Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biology of reproduction 86,27.
    Diaz, F.J., O'Brien, M.J., Wigglesworth, K., Eppig, J.J.,2006. The preantral granulosa cell to cumulus cell transition in the mouse ovary:development of competence to undergo expansion. Developmental biology 299,91-104.
    Diaz, F.J., Wigglesworth, K., Eppig, J.J.,2007. Oocytes determine cumulus cell lineage in mouse ovarian follicles. Journal of cell science 120,1330-1340.
    DiCicco-Bloom, E., Friedman, W.J., Black, I.B.,1993. NT-3 stimulates sympathetic neuroblast proliferation by promoting precursor survival. Neuron 11,1101-1111.
    Dissen, G.A., Garcia-Rudaz, C., Ojeda, S.R.,2009. Role of neurotrophic factors in early ovarian development. Seminars in reproductive medicine 27,24-31.
    Dissen, G.A., Hill, D.F., Costa, M.E., Les Dees, C.W., Lara, H.E., Ojeda, S.R.,1996. A role for trkA nerve growth factor receptors in mammalian ovulation. Endocrinology 137,198-209.
    Dissen, G.A., Hill, D.F., Costa, M.E., Ma, Y.J., Ojeda, S.R.,1991. Nerve growth factor receptors in the peripubertal rat ovary. Mol Endocrinol 5,1642-1650.
    Dissen, G.A., Hirshfield, A.N., Malamed, S., Ojeda, S.R.,1995. Expression of neurotrophins and their receptors in the mammalian ovary is developmentally regulated:changes at the time of folliculogenesis. Endocrinology 136,4681-4692.
    Dissen, G.A., Parrott, J.A., Skinner, M.K., Hill, D.F., Costa, M.E., Ojeda, S.R.,2000. Direct effects of nerve growth factor on thecal cells from antral ovarian follicles. Endocrinology 141,4736-4750.
    Dissen, G.A., Romero, C., Hirshfield, A.N., Ojeda, S.R.,2001. Nerve growth factor is required for early follicular development in the mammalian ovary. Endocrinology 142,2078-2086.
    Dissen, G.A., Romero, C., Paredes, A., Ojeda, S.R.,2002. Neurotrophic control of ovarian development. Microscopy research and technique 59,509-515.
    Dole, G., Nilsson, E.E., Skinner, M.K.,2008. Glial-derived neurotrophic factor promotes ovarian primordial follicle development and cell-cell interactions during folliculogenesis. Reproduction 135,671-682.
    Dong, J., Albertini, D.F., Nishimori, K., Kumar, T.R., Lu, N., Matzuk, M.M.,1996. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383,531-535.
    Dorfman, M.D., Kerr, B., Garcia-Rudaz, C., Paredes, A.H., Dissen, G.A., Ojeda, S.R.,2011. Neurotrophins acting via TRKB receptors activate the JAGGED 1-NOTCH2 cell-cell communication pathway to facilitate early ovarian development. Endocrinology 152,5005-5016.
    Dragovic, R.A., Ritter, L.J., Schulz, S.J., Amato, F., Armstrong, D.T., Gilchrist, R.B.,2005. Role of oocyte-secreted growth differentiation factor 9 in the regulation of mouse cumulus expansion. Endocrinology 146,2798-2806.
    Dragovic, R.A., Ritter, L.J., Schulz, S.J., Amato, F., Thompson, J.G., Armstrong, D.T., Gilchrist, R.B.,2007. Oocyte-secreted factor activation of SMAD 2/3 signaling enables initiation of mouse cumulus cell expansion. Biology of reproduction 76,848-857.
    Dube,F., Amireault, P.,2007. Local serotonergic signaling in mammalian follicles, oocytes and early embryos. Life sciences 81,1627-1637.
    Edson, M.A., Nagaraja, A.K., Matzuk, M.M.,2009. The mammalian ovary from genesis to revelation. Endocrine reviews 30,624-712.
    Edwards, R.H., Rutter, W.J., Hanahan, D.,1989. Directed expression of NGF to pancreatic beta cells in transgenic mice leads to selective hyperinnervation of the islets. Cell 58,161-170.
    Eggert, A., Ikegaki, N., Liu, X., Chou, T.T., Lee, V.M., Trojanowski, J.Q., Brodeur, G.M.,2000. Molecular dissection of TrkA signal transduction pathways mediating differentiation in human neuroblastoma cells. Oncogene 19,2043-2051.
    Elvin, J.A., Clark, A.T., Wang, P., Wolfman, N.M., Matzuk, M.M.,1999a. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Molecular endocrinology 13,1035-1048.
    Elvin, J.A., Yan, C., Wang, P., Nishimori, K., Matzuk, M.M.,1999b. Molecular characterization of the follicle defects in the growth differentiation factor 9-deficient ovary. Molecular endocrinology 13,1018-1034.
    Erickson, G.F., Nakatani, A., Ling, N., Shimasaki, S.,1992. Cyclic changes in insulin-like growth factor-binding protein-4 messenger ribonucleic acid in the rat ovary. Endocrinology 130,625-636.
    Ernfors, P., Wetmore, C., Olson, L., Persson, H.,1990. Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. Neuron 5, 511-526.
    Fedorushchenko, A.N., Koval, T., Khamidov, D.,1996. [The effect of a nerve growth factor from different biological sources on the spontaneous maturation of mouse oocytes and on the parthenogenetic activation of pronucleus formation]. Tsitologiia 38,1211-1216.
    Fedorushchenko, A.N., Koval, T., Khamidov, D.,1999. [The effect of in-situ nerve growth factor from different biological sources on the reinitiation of mouse oocyte meiotic maturation in culture and on parthenogenetic activation]. Ontogenez 30,453-455.
    Ferrari, G., Greene, L.A.,1996. Prevention of neuronal apoptotic death by neurotrophic agents and ganglioside GM1:insights and speculations regarding a common mechanism. Perspectives on developmental neurobiology 3,93-100.
    Flood, M.R., Gage, T.L., Bunch, T.D.,1993. Effect of various growth-promoting factors on preimplantation bovine embryo development in vitro. Theriogenology 39,823-833.
    Fraser, H.M.,2006. Regulation of the ovarian follicular vasculature. Reproductive biology and endocrinology:RB&E 4,18.
    Fulop, C., Salustri, A., Hascall, V.C.,1997. Coding sequence of a hyaluronan synthase homologue expressed during expansion of the mouse cumulus-oocyte complex. Archives of biochemistry and biophysics 337,261-266.
    Fulop, C., Szanto, S., Mukhopadhyay, D., Bardos, T., Kamath, R.V., Rugg, M.S., Day, A.J., Salustri, A., Hascall, V.C., Glant, T.T., Mikecz, K.,2003. Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development 130,2253-2261.
    Garcia-Rudaz, C., Dorfman, M., Nagalla, S., Svechnikov, K., Soder, O., Ojeda, S.R., Dissen, G.A., 2011. Excessive ovarian production of nerve growth factor elicits granulosa cell apoptosis by setting in motion a tumor necrosis factor alpha/stathmin-mediated death signaling pathway. Reproduction 142,319-331.
    Gilchrist, R.B., Lane, M., Thompson, J.G.,2008. Oocyte-secreted factors:regulators of cumulus cell function and oocyte quality. Human reproduction update 14,159-177.
    Gittens, J.E., Kidder, G.M.,2005. Differential contributions of connexin37 and connexin43 to oogenesis revealed in chimeric reaggregated mouse ovaries. Journal of cell science 118,5071-5078.
    Giudice, L.C.,2001. Insulin-like growth factor family in Graafian follicle development and function. Journal of the Society for Gynecologic Investigation 8, S26-29.
    Golden, J.P., DeMaro, J.A., Osborne, P.A., Milbrandt, J., Johnson, E.M., Jr.,1999. Expression of neurturin, GDNF, and GDNF family-receptor mRNA in the developing and mature mouse. Experimental neurology 158,504-528.
    Gosden, R.G., Mullan, J., Picton, H.M., Yin, H., Tan, S.L.,2002. Current perspective on primordial follicle cryopreservation and culture for reproductive medicine. Human reproduction update 8, 105-110.
    Gotz, R., Koster, R., Winkler, C., Raulf,F., Lottspeich,F., Schartl, M., Thoenen, H.,1994. Neurotrophin-6 is a new member of the nerve growth factor family. Nature 372,266-269.
    Grewal, S.S., York, R.D., Stork, P.J.,1999. Extracellular-signal-regulated kinase signalling in neurons. Current opinion in neurobiology 9,544-553.
    Gui, L.M., Joyce, I.M.,2005. RNA interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biology of reproduction 72,195-199.
    Hamanoue, M., Middleton, G., Wyatt, S., Jaffray, E., Hay, R.T., Davies, A.M.,1999. p75-mediated NF-kappaB activation enhances the survival response of developing sensory neurons to nerve growth factor. Molecular and cellular neurosciences 14,28-40.
    Harlow, C.R., Bradshaw, A.C., Rae, M.T., Shearer, K.D., Hillier, S.G.,2007. Oestrogen formation and connective tissue growth factor expression in rat granulosa cells. The Journal of endocrinology 192,41-52.
    Hayashi, K.G., Ushizawa, K., Hosoe, M., Takahashi, T.,2010. Differential genome-wide gene expression profiling of bovine largest and second-largest follicles:identification of genes associated with growth of dominant follicles. Reproductive biology and endocrinology:RB&E 8,11.
    Hempstead, B.L., Rabin, S.J., Kaplan, L., Reid, S., Parada, L.F., Kaplan, D.R.,1992. Overexpression of the trk tyrosine kinase rapidly accelerates nerve growth factor-induced differentiation. Neuron 9,883-896.
    Hernandez-Gonzalez, I., Gonzalez-Robayna, I., Shimada, M., Wayne, C.M., Ochsner, S.A., White, L., Richards, J.S.,2006. Gene expression profiles of cumulus cell oocyte complexes during ovulation reveal cumulus cells express neuronal and immune-related genes:does this expand their role in the ovulation process? Mol Endocrinol 20,1300-1321.
    Hong, S.G., Jang, G., Oh, H.J., Koo, O.J., Park, J.E., Park, H.J., Kang, S.K., Lee, B.C.,2009. The effects of brain-derived neurotrophic factor and metformin on in vitro developmental competence of bovine oocytes. Zygote 17,187-193.
    Hsieh, M., Lee, D., Panigone, S., Homer, K., Chen, R., Theologis, A., Lee, D.C., Threadgill, D.W., Conti, M.,2007. Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation. Molecular and cellular biology 27,1914-1924.
    Hsieh, M., Zamah, A.M., Conti, M.,2009. Epidermal growth factor-like growth factors in the follicular fluid:role in oocyte development and maturation. Seminars in reproductive medicine 27,52-61.
    Huang, E.J., Reichardt, L.F.,2001. Neurotrophins:roles in neuronal development and function. Annual review of neuroscience 24,677-736.
    Huang, E.J., Reichardt, L.F.,2003. Trk receptors:roles in neuronal signal transduction. Annual review of biochemistry 72,609-642.
    Inderdeo, D.S., Edwards, D.R., Han, V.K., Khokha, R.,1996. Temporal and spatial expression of tissue inhibitors of metalloproteinases during the natural ovulatory cycle of the mouse. Biology of reproduction 55,498-508.
    Jana, B., Koszykowska, M., Czarzasta, J.,2011. Expression of nerve growth factor and its receptors, TrkA and p75, in porcine ovaries. The Journal of reproduction and development 57,468-474.
    Jessen, K.R., Mirsky, R.,2008. Negative regulation of myelination:relevance for development, injury, and demyelinating disease. Glia 56,1552-1565.
    Julio-Pieper, M., Lozada, P., Tapia, V., Vega, M., Miranda, C., Vantman, D., Ojeda, S.R., Romero, C.,2009. Nerve growth factor induces vascular endothelial growth factor expression in granulosa cells via a trkA receptor/mitogen-activated protein kinase-extracellularly regulated kinase 2-dependent pathway. The Journal of clinical endocrinology and metabolism 94,3065-3071.
    Kaivo-oja, N., Jeffery, L.A., Ritvos, O., Mottershead, D.G.,2006. Smad signalling in the ovary. Reproductive biology and endocrinology:RB&E 4,21.
    Kalcheim, C., Carmeli, C., Rosenthal, A.,1992. Neurotrophin 3 is a mitogen for cultured neural crest cells. Proceedings of the National Academy of Sciences of the United States of America 89,1661-1665.
    Kaplan, D.R., Miller, F.D.,1997. Signal transduction by the neurotrophin receptors. Current opinion in cell biology 9,213-221.
    Kaplan, D.R., Miller, F.D.,2000. Neurotrophin signal transduction in the nervous system. Current opinion in neurobiology 10,381-391.
    Karkoulias, G., Flordellis, C.,2007. Delayed transactivation of the receptor for nerve growth factor is required for sustained signaling and differentiation by alpha2-adrenergic receptors in transfected PC12 cells. Cellular signalling 19,945-957.
    Kawamura, K., Kawamura, N., Mulders, S.M., Sollewijn Gelpke, M.D., Hsueh, A.J.,2005. Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos. Proceedings of the National Academy of Sciences of the United States of America 102,9206-9211.
    Kawamura, K., Ye, Y., Kawamura, N., Jing, L., Groenen, P., Gelpke, M.S., Rauch, R., Hsueh, A.J., Tanaka, T.,2008. Completion of Meiosis I of preovulatory oocytes and facilitation of preimplantation embryo development by glial cell line-derived neurotrophic factor. Developmental biology 315,189-202.
    Kawashima, I., Liu, Z., Mullany, L.K., Mihara, T., Richards, J.S., Shimada, M.,2012. EGF-Like Factors Induce Expansion of the Cumulus Cell-Oocyte Complexes by Activating Calpain-Mediated Cell Movement. Endocrinology.
    Kerr, B., Garcia-Rudaz, C., Dorfman, M., Paredes, A., Ojeda, S.R.,2009. NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary. Reproduction 138,131-140.
    Klein, R., Jing, S.Q., Nanduri, V., O'Rourke, E., Barbacid, M.,1991. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 65,189-197.
    Koizumi, H., Morita, M., Mikami, S., Shibayama, E., Uchikoshi, T.,1998. Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas. Pathology international 48,93-101.
    Komar, C.M., Matousek, M., Mitsube, K., Mikuni, M., Brannstrom, M., Curry, T.E., Jr.,2001. Effects of genistein on the periovulatory expression of messenger ribonucleic acid for matrix metalloproteinases and tissue inhibitors of metalloproteinases in the rat ovary. Reproduction 121,259-265.
    Lai, K.O., Fu, W.Y., Ip, F.C., Ip, N.Y.,1998. Cloning and expression of a novel neurotrophin, NT-7, from carp. Molecular and cellular neurosciences 11,64-76.
    Lara, H.E., Dees, W.L., Hiney, J.K., Dissen, G.A., Rivier, C., Ojeda, S.R.,1991. Functional recovery of the developing rat ovary after transplantation:contribution of the extrinsic innervation. Endocrinology 129,1849-1860.
    Lara, H.E., Hill, D.F., Katz, K.H., Ojeda, S.R.,1990. The gene encoding nerve growth factor is expressed in the immature rat ovary:effect of denervation and hormonal treatment. Endocrinology 126,357-363.
    Lee, E., Jeong, Y.I., Park, S.M., Lee, J.Y., Kim, J.H., Park, S.W., Hossein, M.S., Jeong, Y.W., Kim, S., Hyun, S.H., Hwang, W.S.,2007. Beneficial effects of brain-derived neurotropic factor on in vitro maturation of porcine oocytes. Reproduction 134,405-414.
    Lee, F.S., Chao, M.V.,2001. Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proceedings of the National Academy of Sciences of the United States of America 98,3555-3560.
    Lee, K.F., Davies, A.M., Jaenisch, R.,1994. p75-deficient embryonic dorsal root sensory and neonatal sympathetic neurons display a decreased sensitivity to NGF. Development 120,1027-1033.
    Lee, R., Kermani, P., Teng, K.K., Hempstead, B.L.,2001. Regulation of cell survival by secreted proneurotrophins. Science 294,1945-1948.
    Levi-Montalcini, R.,1987. The nerve growth factor 35 years later. Science 237,1154-1162.
    Levi-Montalcini, R., Hamburger, V.,'1951. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo. The Journal of experimental zoology 116,321-361.
    Levi-Montalcini, R., Skaper, S.D., Dal Toso, R., Petrelli, L., Leon, A.,1996. Nerve growth factor: from neurotrophin to neurokine. Trends in neurosciences 19,514-520.
    Lewin, G.R., Barde, Y.A.,1996. Physiology of the neurotrophins. Annual review of neuroscience 19,289-317.
    Liang, N., Xu, Y., Tin, Y., Yao, G., Tian, H., Wang, G., Lian, J., Wang, Y, Sun, F.,2011. Steroidogenic factor-1 is required for TGF-beta3-mediated 17beta-estradiol synthesis in mouse ovarian granulosa cells. Endocrinology 152,3213-3225.
    Lin, L.F., Doherty, D.H., Lile, J.D., Bektesh, S., Collins, F.,1993. GDNF:a glial cell line-derived neurotrophic factor formidbrain dopaminergic neurons. Science 260,1130-1132.
    Linher-Melville, K., Li, J.,2013. The roles of glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and nerve growth factor during the final stage of folliculogenesis: a focus on oocyte maturation. Reproduction 145, R43-54.
    Linher, K., Wu, D., Li, J.,2007. Glial cell line-derived neurotrophic factor:an intraovarian factor that enhances oocyte developmental competence in vitro. Endocrinology 148,4292-4301.
    Liu, J., Linher, K., Li, J.,2009a. Porcine DAZL messenger RNA:its expression and regulation during oocyte maturation. Molecular and cellular endocrinology 311,101-108.
    Liu, Z., de Matos, D.G., Fan, H.Y., Shimada, M., Palmer, S., Richards, J.S.,2009b. Interleukin-6: an autocrine regulator of the mouse cumulus cell-oocyte complex expansion process. Endocrinology 150,3360-3368.
    Liu, Z., Fan, H.Y., Wang, Y, Richards, J.S.,2010. Targeted disruption of Mapk14 (p38MAPKalpha) in granulosa cells and cumulus cells causes cell-specific changes in gene expression profiles that rescue COC expansion and maintain fertility. Molecular endocrinology 24,1794-1804.
    Lommatzsch, M., Schloetcke, K., Klotz, J., Schuhbaeck, K., Zingler, D., Zingler, C., Schulte-Herbruggen, O., Gill, H., Schuff-Werner, P., Virchow, J.C.,2005. Brain-derived neurotrophic factor in platelets and airflow limitation in asthma. American journal of respiratory and critical care medicine 171,115-120.
    Lorenzo, P.L., Rebollar, P.G., Illera, M.J,, Illera, J.C., Illera, M., Alvarino, J.M.,1996. Stimulatory effect of insulin-like growth factor I and epidermal growth factor on the maturation of rabbit oocytes in vitro. Journal of reproduction and fertility 107,109-117.
    Lou, X., Yano, H., Lee, F., Chao, M.V., Farquhar, M.G.,2001. GIPC and GAIP form a complex with TrkA:a putative link between G protein and receptor tyrosine kinase pathways. Molecular biology of the cell 12,615-627.
    Lu, B., Pang, P.T., Woo, N.H.,2005. The yin and yang of neurotrophin action. Nature reviews. Neuroscience 6,603-614.
    MacPhee, I., Barker, P.A.,1999. Extended ceramide exposure activates the trkA receptor by increasing receptor homodimer formation. Journal of neurochemistry 72,1423-1430.
    Malamed, S., Gibney, J.A., Ojeda, S.R.,1992. Ovarian innervation develops before initiation of folliculogenesis in the rat. Cell and tissue research 270,87-93.
    Martins da Silva, S.J., Gardner, J.O., Taylor, J.E., Springbett, A., De Sousa, P.A., Anderson, R.A., 2005. Brain-derived neurotrophic factor promotes bovine oocyte cytoplasmic competence for embryo development. Reproduction 129,423-434.
    Matrisian, L.M.,1990. Metalloproteinases and their inhibitors in matrix remodeling. Trends in genetics:TIG 6,121-125.
    Mayerhofer, A., Dissen, G.A., Parrott, J.A., Hill, D.F., Mayerhofer, D., Garfield, R.E., Costa, M.E., Skinner, M.K., Ojeda, S.R.,1996. Involvement of nerve growth factor in the ovulatory cascade: trkA receptor activation inhibits gap junctional communication between thecal cells. Endocrinology 137,5662-5670.
    Mazerbourg, S., Bondy, C.A., Zhou, J., Monget, P.,2003. The insulin-like growth factor system:a key determinant role in the growth and selection of ovarian follicles? a comparative species study. Reproduction in domestic animals= Zuchthygiene 38,247-258.
    McElroy, S.L., Byrne, J.A., Chavez, S.L., Benr, B., Hsueh, A.J., Westphal, L.M., Pera, R.A.,2010. Parthenogenic blastocysts derived from cumulus-free in vitro matured human oocytes. PloS one 5, e10979.
    McRae, R.S., Johnston, H.M., Mihm, M., O'Shaughnessy, P.J.,2005. Changes in mouse granulosa cell gene expression during early luteinization. Endocrinology 146,309-317.
    Micera, A., Lambiase, A., Stampachiacchiere, B., Sgrulletta, R., Normando, E.M., Bonini, S., Bonini, S.,2007. Nerve growth factor has a modulatory role on human primary fibroblast cultures derived from vernal keratoconjunctivitis-affected conjunctiva. Molecular vision 13, 981-987.
    Micera, A., Vigneti, E., Pickholtz, D., Reich, R., Pappo, O., Bonini, S., Maquart, F.X., Aloe, L., Levi-Schaffer, F.,2001. Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair. Proceedings of the National Academy of Sciences of the United States of America 98,6162-6167.
    Monget, P., Bondy, C.,2000. Importance of the IGF system in early folliculogenesis. Molecular and cellular endocrinology 163,89-93.
    Monteleone, P., Artini, P.G., Simi, G., Cela, V., Casarosa, E., Begliuomini, S., Ninni, F., Pluchino, N., Luisi, M., Genazzani, A.R.,2007. Brain derived neurotrophic factor circulating levels in patients undergoing IVF. Journal of assisted reproduction and genetics 24,477-480.
    Moore, R.K., Otsuka, F., Shimasaki, S.,2003. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. The Journal of biological chemistry 278,304-310.
    Muragaki, Y, Chou, T.T., Kaplan, D.R., Trojanowski, J.Q., Lee, V.M.,1997. Nerve growth factor induces apoptosis in human medulloblastoma cell lines that express TrkA receptors. The Journal of neuroscience:the official journal of the Society for Neuroscience 17,530-542.
    Mutoh, T., Tokuda, A., Inokuchi, J., Kuriyama, M.,1998. Glucosylceramide synthase inhibitor inhibits the action of nerve growth factor in PC 12 cells. The Journal of biological chemistry 273,26001-26007.
    Myers, M., Pangas, S.A.,2010. Regulatory roles of transforming growth factor beta family members in folliculogenesis. Wiley interdisciplinary reviews. Systems biology and medicine 2,117-125.
    Nebreda, A.R., Martin-Zanca, D., Kaplan, D.R., Parada, L.F., Santos, E.,1991. Induction by NGF of meiotic maturation of Xenopus oocytes expressing the trk proto-oncogene product. Science 252,558-561.
    Nothnick, W.B.,2000. Disruption of the tissue inhibitor of metalloproteinase-1 gene results in altered reproductive cyclicity and uterine morphology in reproductive-age female mice. Biology of reproduction 63,905-912.
    Nothnick, W.B., Soloway, P., Curry, T.E., Jr.,1997. Assessment of the role of tissue inhibitor of metalloproteinase-1 (TIMP-1) during the periovulatory period in female mice lacking a functional TIMP-1 gene. Biology of reproduction 56,1181-1188.
    Nuttinck, F., Marquant-Le Guienne, B., Clement, L., Reinaud, P., Charpigny, G., Grimard, B.,2008. Expression of genes involved in prostaglandin E2 and progesterone production in bovine cumulus-oocyte complexes during in vitro maturation and fertilization. Reproduction 135,593-603.
    Nyholt de Prada, J.K., Lee, Y.S., Latham, K.E., Chaffin, C.L., VandeVoort, C.A.,2009. Role for cumulus cell-produced EGF-like ligands during primate oocyte maturation in vitro. American journal of physiology. Endocrinology and metabolism 296, E1049-1058.
    Ojeda, S.R., Romero, C., Tapia, V., Dissen, G.A.,2000. Neurotrophic and cell-cell dependent control of early follicular development. Molecular and cellular endocrinology 163,67-71.
    Orike, N., Thrasivoulou, C., Wrigley, A., Cowen, T.,2001. Differential regulation of survival and growth in adult sympathetic neurons:an in vitro study of neurotrophin responsiveness. Journal of neurobiology 47,295-305.
    Osteen, K.G., Yeaman, G.R., Bruner-Tran, K.L.,2003. Matrix metalloproteinases and endometriosis. Seminars in reproductive medicine 21,155-164.
    Otsuka,F., McTavish, K.J., Shimasaki, S.,2011. Integral role of GDF-9 and BMP-15 in ovarian function. Molecular reproduction and development 78,9-21.
    Pangas, S.A.,2012. Bone morphogenetic protein signaling transcription factor (SMAD) function in granulosa cells. Molecular and cellular endocrinology 356,40-47.
    Papp, A.B., Somfai, T., Tartaglione, M., Varga, E., Gardon, J.C.,2005. The effect of nerve growth factor on nuclear progression of porcine oocytes during in vitro maturation and embryo development. Acta veterinaria Hungarica 53,91-101.
    Paredes, A., Romero, C., Dissen, G.A., DeChiara, T.M., Reichardt, L., Cornea, A., Ojeda, S.R., Xu, B.,2004. TrkB receptors are required for follicular growth and oocyte survival in the mammalian ovary. Developmental biology 267,430-449.
    Park, J.Y., Su, Y.Q., Ariga, M., Law, E., Jin, S.L., Conti, M.,2004. EGF-like growth factors as mediators of LH action in the ovulatory follicle. Science 303,682-684.
    Pezet, S., Malcangio, M.,2004. Brain-derived neurotrophic factor as a drug target for CNS disorders. Expert opinion on therapeutic targets 8,391-399.
    Pluchino, N., Cubeddu, A., Begliuomini, S., Merlini, S., Giannini, A., Bucci,F., Casarosa, E., Luisi, M., Cela, V., Genazzani, A.R.,2009. Daily variation of brain-derived neurotrophic factor and cortisol in women with normal menstrual cycles, undergoing oral contraception and in postmenopause. Human reproduction 24,2303-2309.
    Prakash, Y, Thompson, M.A., Meuchel, L., Pabelick, C.M., Mantilla, C.B., Zaidi, S., Martin, R.J., 2010. Neurotrophins in lung health and disease. Expert review of respiratory medicine 4,395-411.
    Prochazka, R., Petlach, M., Nagyova, E., Nemcova, L.,2011. 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 141,425-435.
    Purves, D., Snider, W.D., Voyvodic, J.T.,1988. Trophic regulation of nerve cell morphology and innervation in the autonomic nervous system. Nature 336,123-128.
    Qian, X., Ginty, D.D.,2001. SH2-B and APS are multimeric adapters that augment TrkA signaling. Molecular and cellular biology 21,1613-1620.
    Reich, R., Tsafriri, A., Mechanic, G.L.,1985. The involvement of collagenolysis in ovulation in the rat. Endocrinology 116,522-527.
    Reizel, Y., Elbaz, J., Dekel, N.,2010. Sustained activity of the EGF receptor is an absolute requisite for LH-induced oocyte maturation and cumulus expansion. Mol Endocrinol 24,402-411.
    Reynolds, N., Collier, B., Bingham, V., Gray, N.K., Cooke, H.J.,2007. Translation of the synaptonemal complex component Sycp3 is enhanced in vivo by the germ cell specific regulator Dazl. Rna 13,974-981.
    Rezaee, F., Rellick, S.L., Piedimonte, G., Akers, S.M., O'Leary, H.A., Martin, K., Craig, M.D., Gibson, L.F.,2010. Neurotrophins regulate bone marrow stromal cell IL-6 expression through the MAPK pathway. PloS one 5, e9690.
    Richards, J.S.,2005. Ovulation:new factors that prepare the oocyte for fertilization. Molecular and cellular endocrinology 234,75-79.
    Richards, J.S.,2007. Genetics of ovulation. Seminars in reproductive medicine 25,235-242.
    Richards, J.S., Liu, Z., Shimada, M.,2008. Immune-like mechanisms in ovulation. Trends in endocrinology and metabolism:TEM 19,191-196.
    Roh, J.S., Bondestam, J., Mazerbourg, S., Kaivo-Oja, N., Groome, N., Ritvos, O., Hsueh, A.J.,2003. Growth differentiation factor-9 stimulates inhibin production and activates Smad2 in cultured rat granulosa cells. Endocrinology 144,172-178.
    Rojas, M., Yao, S., Lin, Y.Z.,1996. Controlling epidermal growth factor (EGF)-stimulated Ras activation in intact cells by a cell-permeable peptide mimicking phosphorylated EGF receptor. The Journal of biological chemistry 271,27456-27461.
    Romero, C., Paredes, A., Dissen, G.A., Ojeda, S.R.,2002. Nerve growth factor induces the expression of functional FSH receptors in newly formed follicles of the rat ovary. Endocrinology 143,1485-1494.
    Romero, S., Smitz, J.,2009. Epiregulin can effectively mature isolated cumulus-oocyte complexes, but fails as a substitute for the hCG/epidermal growth factor stimulus on cultured follicles. Reproduction 137,997-1005.
    Rush, R.A., Chie, E., Liu, D., Tafreshi, A., Zettler, C., Zhou, X.F.,1997. Neurotrophic factors are required by mature sympathetic neurons for survival, transmission and connectivity. Clinical and experimental pharmacology & physiology 24,549-555.
    Russell, D.L., Robker, R.L.,2007. Molecular mechanisms of ovulation:co-ordination through the cumulus complex. Human reproduction update 13,289-312.
    Sadeu, J.C., Doedee, A.M., Neal, M.S., Hughes, E.G., Foster, W.G.,2012. Neurotrophins (BDNF and NGF) in follicular fluid of women with different infertility diagnoses. Reproductive biomedicine online 24,174-179.
    Salas, C., Julio-Pieper, M., Valladares, M., Pommer, R., Vega, M., Mastronardi, C., Kerr, B., Ojeda, S.R., Lara, H.E., Romero, C.,2006. Nerve growth factor-dependent activation of trkA receptors in the human ovary results in synthesis of follicle-stimulating hormone receptors and estrogen secretion. The Journal of clinical endocrinology and metabolism 91,2396-2403.
    Salustri, A., Garlanda, C., Hirsch, E., De Acetis, M., Maccagno, A., Bottazzi, B., Doni, A., Bastone, A., Mantovani, G., Beck Peccoz, P., Salvatori, G., Mahoney, D.J., Day, A.J., Siracusa, G., Romani, L., Mantovani, A.,2004. PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 131,1577-1586.
    Salustri, A., Yanagishita, M., Hascall, V.C.,1990. Mouse oocytes regulate hyaluronic acid synthesis and mucification by FSH-stimulated cumulus cells. Developmental biology 138,26-32.
    Sasseville, M., Ritter, L.J., Nguyen, T.M., Liu,F., Mottershead, D.G., Russell, D.L., Gilchrist, R.B., 2010. Growth differentiation factor 9 signaling requires ERK1/2 activity in mouse granulosa and cumulus cells. Journal of cell science 123,3166-3176.
    Sato, E.,1998. Morphological dynamics of cumulus-oocyte complex during oocyte maturation. Italian journal of anatomy and embryology= Archivio italiano di anatomia ed embriologia 103, 103-118.
    Schlessinger, J., Ullrich, A.,1992. Growth factor signaling by receptor tyrosine kinases. Neuron 9, 383-391.
    Schramm, A., Schulte, J.H., Astrahantseff, K., Apostolov, O., Limpt, V., Sieverts, H., Kuhfittig-Kulle, S., Pfeiffer, P., Versteeg, R., Eggert, A.,2005. Biological effects of TrkA and TrkB receptor signaling in neuroblastoma. Cancer letters 228,143-153.
    Schulte, J.H., Schramm, A., Klein-Hitpass, L., Klenk, M., Wessels, H., Hauffa, B.P., Eils, J., Eils, R., Brodeur, G.M., Schweigerer, L., Havers, W., Eggert, A.,2005. Microarray analysis reveals differential gene expression patterns and regulation of single target genes contributing to the opposing phenotype of TrkA- and TrkB-expressing neuroblastomas. Oncogene 24,165-177.
    Segal, R.A.,2003. Selectivity in neurotrophin signaling:theme and variations. Annual review of neuroscience 26,299-330.
    Segers, I., Adriaenssens, T., Wathlet, S., Smitz, J.,2012. Gene expression differences induced by equimolar low doses of LH or hCG in combination with FSH in cultured mouse antral follicles. The Journal of endocrinology 215,269-280.
    Sehgal, A., Wall, D.A., Chao, M.V.,1988. Efficient processing and expression of human nerve growth factor receptors in Xenopus laevis oocytes:effects on maturation. Molecular and cellular biology 8,2242-2246.
    Seidah, N.G., Benjannet, S., Pareek, S., Chretien, M., Murphy, R.A.,1996. Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS letters 379,247-250.
    Seifer, D.B., Feng, B., Shelden, R.M., Chen, S., Dreyfus, C.F.,2002a. Brain-derived neurotrophic factor:a novel human ovarian follicular protein. The Journal of clinical endocrinology and metabolism 87,655-659.
    Seifer, D.B., Feng, B., Shelden, R.M., Chen, S., Dreyfus, C.F.,2002b. Neurotrophin-4/5 and neurotrophin-3 are present within the human ovarian follicle but appear to have different paracrine/autocrine functions. The Journal of clinical endocrinology and metabolism 87,4569-4571.
    Seli, E., Berkkanoglu, M., Arici, A.,2003. Pathogenesis of endometriosis. Obstetrics and gynecology clinics of North America 30,41-61.
    Sherrard, R.M., Bower, A.J.,2002. Climbing fiber development:do neurotrophins have a part to play? Cerebellum 1,265-275.
    Shimada, M., Hernandez-Gonzalez, I., Gonzalez-Robayna, I., Richards, J.S.,2006. 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. Molecular endocrinology 20,1352-1365.
    Shimasaki, S., Moore, R.K., Erickson, G.F., Otsuka, F.,2003. The role of bone morphogenetic proteins in ovarian function. Reprod Suppl 61,323-337.
    Siu, M.K., Wong, O.G., Cheung, A.N.,2009. TrkB as a therapeutic target for ovarian cancer. Expert opinion on therapeutic targets 13,1169-1178.
    Snider, W.D.,1994. Functions of the neurotrophins during nervous system development:what the knockouts are teaching us. Cell 77,627-638.
    Solc, P., Schultz, R.M., Motlik, J.,2010. Prophase I arrest and progression to metaphase I in mouse oocytes:comparison of resumption of meiosis and recovery from G2-arrest in somatic cells. Molecular human reproduction 16,654-664.
    Son, W.Y., Das, M., Shalom-Paz, E., Holzer, H.,2011. Mechanisms of follicle selection and development. Minerva ginecologica 63,89-102.
    Spears, N., Molinek, M.D., Robinson, L.L., Fulton, N., Cameron, H., Shimoda, K., Telfer, E.E., Anderson, R.A., Price, D.J.,2003. The role of neurotrophin receptors in female germ-cell survival in mouse and human. Development 130,5481-5491.
    Stilley, J.A., Sharpe-Timms, K.L.,2012. TIMP1 contributes to ovarian anomalies in both an MMP-dependent and -independent manner in a rat model. Biology of reproduction 86,47.
    Stilley, J.A., Woods-Marshall, R., Sutovsky, M., Sutovsky, P., Sharpe-Timms, K.L.,2009. Reduced fecundity in female rats with surgically induced endometriosis and in their daughters:a potential role for tissue inhibitors of metalloproteinase 1. Biology of reproduction 80,649-656.
    Stouffer, R.L., Xu, F., Duffy, D.M.,2007. Molecular control of ovulation and luteinization in the primate follicle. Frontiers in bioscience:a journal and virtual library 12,297-307.
    Su, Y.Q., Denegre, J.M., Wigglesworth, K., Pendola, F.L., O'Brien, M.J., Eppig, J.J.,2003. Oocyte-dependent activation of mitogen-activated protein kinase (ERK1/2) in cumulus cells is required for the maturation of the mouse oocyte-cumulus cell complex. Developmental biology 263, 126-138.
    Su, Y.Q., Wigglesworth, K., Pendola, F.L., O'Brien, M.J., Eppig, J.J.,2002. Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse. Endocrinology 143,2221-2232.
    Su, Y.Q., Wu, X., O'Brien, M.J., Pendola, F.L., Denegre, J.N., Matzuk, M.M., Eppig, J.J.,2004. Synergistic roles of BMP15 and GDF9 in the development and function of the oocyte-cumulus cell complex in mice:genetic evidence for an oocyte-granulosa cell regulatory loop. Developmental biology 276,64-73.
    Sugiura, K., Su, Y.Q., Eppig, J.J.,2009. Targeted suppression of Has2 mRNA in mouse cumulus cell-oocyte complexes by adenovirus-mediated short-hairpin RNA expression. Molecular reproduction and development 76,537-547.
    Takahashi, M.,2001. The GDNF/RET signaling pathway and human diseases. Cytokine & growth factor reviews 12,361-373.
    Tapia, V., Gabler, F., Munoz, M., Yazigi, R., Paredes, A., Selman, A., Vega, M., Romero, C.,2011. Tyrosine kinase A receptor (trkA):a potential marker in epithelial ovarian cancer. Gynecologic oncology 121,13-23.
    Teng, H.K., Teng, K.K., Lee, R., Wright, S., Tevar, S., Almeida, R.D., Kermani, P., Torkin, R., Chen, Z.Y., Lee, F.S., Kraemer, R.T., Nykjaer, A., Hempstead, B.L.,2005. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. The Journal of neuroscience:the official journal of the Society for Neuroscience 25,5455-5463.
    Tessarollo, L.,1998. Pleiotropic functions of neurotrophins in development. Cytokine & growth factor reviews 9,125-137.
    Tomac, A., Lindqvist, E., Lin, L.F., Ogren, S.O., Young, D., Hoffer, B.J., Olson, L.,1995. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 373,335-339.
    Toran-Allerand, C.D.,1996a. The estrogen/neurotrophin connection during neural development:is co-localization of estrogen receptors with the neurotrophins and their receptors biologically relevant? Developmental neuroscience 18,36-48.
    Toran-Allerand, C.D.,1996b. Mechanisms of estrogen action during neural development:mediation by interactions with the neurotrophins and their receptors? The Journal of steroid biochemistry and molecular biology 56,169-178.
    Uhlenhaut, N.H., Treier, M.,2006. Foxl2 function in ovarian development. Molecular genetics and metabolism 88,225-234.
    Ulrich, E., Duwel, A., Kauffmann-Zeh, A., Gilbert, C., Lyon, D., Rudkin, B., Evan, G., Martin-Zanca, D.,1998. Specific TrkA survival signals interfere with different apoptotic pathways. Oncogene 16,825-832.
    Valve, E., Penttila, T.L., Paranko, J., Harkonen, P.,1997. FGF-8 is expressed during specific phases of rodent oocyte and spermatogonium development. Biochemical and biophysical research communications 232,173-177.
    Vanderhyden, B.C., Caron, P.J., Buccione, R., Eppig, J.J.,1990. Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation. Developmental biology 140,307-317.
    Varani, S., Elvin, J.A., Yan, C., DeMayo, J., DeMayo, F.J., Horton, H.F., Byrne, M.C., Matzuk, M.M.,2002. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 16,1154-1167.
    Wang, H., Wen, Y., Mooney, S., Li, H., Behr, B., Polan, M.L.,2003. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression in human preimplantation embryos. Fertility and sterility 80 Suppl 2,736-742.
    Wayne, C.M., Fan, H.Y., Cheng, X., Richards, J.S.,2007. Follicle-stimulating hormone induces multiple signaling cascades:evidence that activation of Rous sarcoma oncogene, RAS, and the epidermal growth factor receptor are critical for granulosa cell differentiation. Molecular endocrinology 21,1940-1957.
    Widenfalk, J., Parvinen, M., Lindqvist, E., Olson, L.,2000. Neurturin, RET, GFRalpha-1 and GFRalpha-2, but not GFRalpha-3, mRNA are expressed in mice gonads. Cell and tissue research 299,409-415.
    Yamashita, Y., Okamoto, M., Kawashima, I., Okazaki, T., Nishimura, R., Gunji, Y., Hishinuma, M., Shimada, M.,2011. Positive feedback loop between prostaglandin E2 and EGF-like factors is essential for sustainable activation of MAPK3/1 in cumulus cells during in vitro maturation of porcine cumulus oocyte complexes. Biology of reproduction 85,1073-1082.
    Yan, C., Wang, P., DeMayo, J., DeMayo, F.J., Elvin, J.A., Carino, C., Prasad, S.V., Skinner, S.S., Dunbar, B.S., Dube, J.L., Celeste, A.J., Matzuk, M.M.,2001. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Molecular endocrinology 15,854-866.
    Yao, R., Cooper, G.M.,1995. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267,2003-2006.
    Yoshino, O., McMahon, H.E., Sharma, S., Shimasaki, S.,2006. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Proceedings of the National Academy of Sciences of the United States of America 103,10678-10683.
    Yu, X., Liu, L., Cai, B., He, Y., Wan, X.,2008. Suppression of anoikis by the neurotrophic receptor TrkB in human ovarian cancer. Cancer science 99,543-552.
    Zhang, L., Li, J., Su, P., Xiong, C.,2010. The role of brain-derived neurotrophic factor in mouse oocyte maturation in vitro. Journal of Huazhong University of Science and Technology. Medical sciences= Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban= Huazhong keji daxue xuebao. Yixue Yingdewen ban 30,781-785.
    Zhao, P., Qiao, J., Huang, S., Zhang, Y., Liu, S., Yan, L.Y., Hsueh, A.J., Duan, E.K.,2011. Gonadotrophin-induced paracrine regulation of human oocyte maturation by BDNF and GDNF secreted by granulosa cells. Human reproduction 26,695-702.
    Zhuo, L., Kimata, K.,2001. Cumulus oophorus extracellular matrix:its construction and regulation. Cell structure and function 26,189-196.