Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Stem cell factor promotes in vitro ovarian follicle development in the domestic cat by upregulating c-kit mRNA expression and stimulating the phosphatidylinositol 3-kinase/AKT pathway

Paweena Thuwanut A C , Pierre Comizzoli A , David E. Wildt A , Carol L. Keefer B and Nucharin Songsasen A D
+ Author Affiliations
- Author Affiliations

A Smithsonian Conservation Biology Institute, National Zoological Park, Front Royal, VA 22630 and Washington, DC 20008, USA.

B Department of Animal and Avian Sciences, University of Maryland, College Park, MD 20740, USA.

C Present address: Department of Obstetrics, Gynaecology and Reproduction, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.

D Corresponding author. Email: songsasenn@si.edu

Reproduction, Fertility and Development 29(7) 1356-1368 https://doi.org/10.1071/RD16071
Submitted: 11 February 2016  Accepted: 3 May 2016   Published: 9 June 2016

Abstract

In the present study we examined the effects of stem cell factor (SCF; 50 vs 100 ng mL–1) alone or in combination with epidermal growth factor (EGF; 100 ng mL–1) on: (1) the in vitro viability and growth of cat follicles within ovarian cortices; (2) phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) phosphorylation; and (3) c-kit and FSH receptor (FSHr) mRNA expression. At 100 ng mL–1, SCF increased (P ≤ 0.05) the percentage and size of secondary follicles after 14 days of in vitro culture and sustained AKT phosphorylation after 3 days incubation. EGF suppressed this beneficial effect and reduced (P ≤ 0.05) the percentage of structurally normal follicles and FSHr expression when combined with 100 ng mL–1 SCF. Expression of c-kit mRNA was higher (P ≤ 0.05) in the presence of 100 ng mL–1 SCF compared with fresh follicles and cohorts cultured under other conditions. A c-kit inhibitor suppressed follicle growth and reduced AKT phosphorylation. Collectively, the results demonstrate that SCF promotes cat follicle development by upregulating c-kit mRNA expression and AKT phosphorylation. EGF suppresses the stimulating effect of SCF, leading to downregulation of FSHr expression.

Additional keywords: folliculogenesis, gene expression, growth factor, ovary.


References

Bristol, S. K., and Woodruff, T. K. (2004). Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary. Biol. Reprod. 70, 846–859.
Follicle-restricted compartmentalization of transforming growth factor beta superfamily ligands in the feline ovary.CrossRef | 1:CAS:528:DC%2BD2cXhs1Chtrw%3D&md5=a03740043575c92233d619499f400230CAS | 14656728PubMed |

Bristol-Gould, S., and Woodruff, T. K. (2006). Folliculogenesis in the domestic cat (Felis catus). Theriogenology 66, 5–13.
Folliculogenesis in the domestic cat (Felis catus).CrossRef | 1:CAS:528:DC%2BD28XlsFKrsLo%3D&md5=e5327284e4262d617de4c2fea60d837eCAS | 16620931PubMed |

Brown, C., LaRocca, J., Pietruska, J., Ota, M., Anderson, L., Smith, S. D., Weston, P., Rasoulpour, T., and Hixon, M. L. (2010). Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1. Biol. Reprod. 82, 246–256.
Subfertility caused by altered follicular development and oocyte growth in female mice lacking PKB alpha/Akt1.CrossRef | 1:CAS:528:DC%2BC3cXhsVSns7Y%3D&md5=0610977ca5faafd4ffa070b714a89606CAS | 19794155PubMed |

Cantley, L. C. (2002). The phosphoinositide 3-kinase pathway. Science 296, 1655–1657.
The phosphoinositide 3-kinase pathway.CrossRef | 1:CAS:528:DC%2BD38XktlChu7s%3D&md5=0585faa42b26c44d0b8e034e26c14c38CAS | 12040186PubMed |

Carlsson, I. B., Laitinen, M. P., Scott, J. E., Louhio, H., Velentzis, L., Tuuri, T., Aaltonen, J., Ritvos, O., Winston, R. M., and Hovatta, O. (2006). Kit ligand and c-Kit are expressed during early human ovarian follicular development, and their interaction is required for the survival of follicles in long-term culture. Reproduction 131, 641–649.
Kit ligand and c-Kit are expressed during early human ovarian follicular development, and their interaction is required for the survival of follicles in long-term culture.CrossRef | 1:CAS:528:DC%2BD28XltV2jtr4%3D&md5=2934fdc1e930a167780950a96d60f038CAS | 16595715PubMed |

Celestino, J. J. H., Matos, M. T. H., and Saraiva, M. V. A. (2009). Regulation of ovarian folliculogenesis by Kit Ligand and the c-Kit system in mammals. Anim. Reprod. 6, 431–439.

Choi, Y., and Rajkovic, A. (2006). Genetics of early mammalian folliculogenesis. Cell. Mol. Life Sci. 63, 579–590.
Genetics of early mammalian folliculogenesis.CrossRef | 1:CAS:528:DC%2BD28XjtVant74%3D&md5=6eee23a3fdc25a669ad59e714a1e4a00CAS | 16416028PubMed |

Clark, D. E., Tisdall, D. J., Fidler, A. E., and McNatty, K. P. (1996). Localization of mRNA encoding c-kit during the initiation of folliculogenesis in ovine fetal ovaries. J. Reprod. Fertil. 106, 329–335.
Localization of mRNA encoding c-kit during the initiation of folliculogenesis in ovine fetal ovaries.CrossRef | 1:CAS:528:DyaK28XitFKnt70%3D&md5=2f02a7ac7a1057fae44cde4f7dcc6d85CAS | 8699418PubMed |

Comizzoli, P., Pukazhenthi, B. S., and Wildt, D. E. (2011). The competence of germinal vesicle oocytes is unrelated to nuclear chromatin configuration and strictly depends on cytoplasmic quantity and quality in the cat model. Hum. Reprod. 26, 2165–2177.
The competence of germinal vesicle oocytes is unrelated to nuclear chromatin configuration and strictly depends on cytoplasmic quantity and quality in the cat model.CrossRef | 1:STN:280:DC%2BC3MnosVagsQ%3D%3D&md5=3585523f7bd390166304afd21efc82ddCAS | 21665874PubMed |

Craig, J., Orisaka, M., Wang, H., Orisaka, S., Thompson, W., Zhu, C., Kotsuji, F., and Tsang, B. K. (2007). Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death. Front. Biosci. 12, 3628–3639.
Gonadotropin and intra-ovarian signals regulating follicle development and atresia: the delicate balance between life and death.CrossRef | 1:CAS:528:DC%2BD2sXms1Kmtbg%3D&md5=45e9e1f7f61fc3da4f698b9edc1f05bdCAS | 17485326PubMed |

Dank, G., Chien, M. B., and London, C. A. (2002). Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats. Am. J. Vet. Res. 63, 1129–1133.
Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats.CrossRef | 1:CAS:528:DC%2BD38XmsF2qs7g%3D&md5=8d90e20d3eabb102e666b49e5fc6a268CAS | 12171166PubMed |

Driancourt, M. A., Reynaud, K., Cortvrindt, R., and Smitz, J. (2000). Roles of KIT and KIT LIGAND in ovarian function. Rev. Reprod. 5, 143–152.
Roles of KIT and KIT LIGAND in ovarian function.CrossRef | 1:CAS:528:DC%2BD3cXnt1altLc%3D&md5=46c26e442c38c2f9ea4e0291194a558fCAS | 11006164PubMed |

Fujihara, M., Comizzoli, P., Wildt, D. E., and Songsasen, N. (2012). Cat and dog primordial follicles enclosed in ovarian cortex sustain viability after in vitro culture on agarose gel in a protein-free medium. Reprod. Domest. Anim. 47, 102–108.
Cat and dog primordial follicles enclosed in ovarian cortex sustain viability after in vitro culture on agarose gel in a protein-free medium.CrossRef | 23279476PubMed |

Fujihara, M., Comizzoli, P., Keefer, C. L., Wildt, D. E., and Songsasen, N. (2014). Epidermal growth factor (EGF) sustains in vitro primordial follicle viability by enhancing stromal cell proliferation via MAPK and PI3K pathways in the prepubertal, but not adult cat ovary. Biol. Reprod. 90, 86.
Epidermal growth factor (EGF) sustains in vitro primordial follicle viability by enhancing stromal cell proliferation via MAPK and PI3K pathways in the prepubertal, but not adult cat ovary.CrossRef | 24554736PubMed |

Galli, S. J., Zsebo, K. M., and Geissler, E. N. (1993). The kit ligand, stem cell factor. Adv. Immunol. 55, 1–96.
The kit ligand, stem cell factor.CrossRef |

Gebauer, G., Peter, A. T., Onesime, D., and Dhanasekaran, N. (1999). Apoptosis of ovarian granulosa cells: correlation with the reduced activity of ERK-signaling module. J. Cell. Biochem. 75, 547–554.
Apoptosis of ovarian granulosa cells: correlation with the reduced activity of ERK-signaling module.CrossRef | 1:CAS:528:DyaK1MXnt1Cjtrs%3D&md5=f112bca7428553988b60e4315b6fc4c0CAS | 10572238PubMed |

Goto, M., Iwase, A., Ando, H., Kurotsuchi, S., Harata, T., and Kikkawa, F. (2007). PTEN and Akt expression during growth of human ovarian follicles. J. Assist. Reprod. Genet. 24, 541–546.
PTEN and Akt expression during growth of human ovarian follicles.CrossRef | 17999178PubMed |

Heinrich, M. C., Griffith, D. J., Druker, B. J., Wait, C. L., Ott, K. A., and Zigler, A. J. (2000). Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 96, 925–932.
| 1:CAS:528:DC%2BD3cXltlKitLw%3D&md5=7b4592c6abf10491136970a769dffd09CAS | 10910906PubMed |

Hobbs, R. J., Howard, J., Wildt, D. E., and Comizzoli, P. (2012). Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro. Reproduction 144, 111–122.
Absence of seasonal changes in FSHR gene expression in the cat cumulus–oocyte complex in vivo and in vitro.CrossRef | 1:CAS:528:DC%2BC38XhtV2ht7vK&md5=71149e10424a7b706c599584a5327a8aCAS | 22596062PubMed |

Hutt, K. J., McLaughlin, E. A., and Holland, M. K. (2006). KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and murine ovarian follicle activation and oocyte growth. Biol. Reprod. 75, 421–433.
KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and murine ovarian follicle activation and oocyte growth.CrossRef | 1:CAS:528:DC%2BD28XovVWmurw%3D&md5=234215c79ac1655868419011fac739e5CAS | 16790689PubMed |

Irusta, G., Abramovich, D., Parborell, F., and Tesone, M. (2010). Direct survival role of vascular endothelial growth factor (VEGF) on rat ovarian follicular cells. Mol. Cell. Endocrinol. 325, 93–100.
Direct survival role of vascular endothelial growth factor (VEGF) on rat ovarian follicular cells.CrossRef | 1:CAS:528:DC%2BC3cXos1yku7g%3D&md5=006bb831054d5dcbd5f2bc7ab2ae09e7CAS | 20417686PubMed |

Jewgenow, K., and Paris, M. C. (2006). Preservation of female germ cells from ovaries of cat species. Theriogenology 66, 93–100.
Preservation of female germ cells from ovaries of cat species.CrossRef | 16620936PubMed |

Kidder, G. M., and Mhawi, A. A. (2002). Gap junctions and ovarian folliculogenesis. Reproduction 123, 613–620.
Gap junctions and ovarian folliculogenesis.CrossRef | 1:CAS:528:DC%2BD38XjvVGgtL8%3D&md5=c6ae1ae748b6cefc69fa17798a64b8e8CAS | 12006089PubMed |

Lima, I. M., Brito, I. R., Rodrigues, G. Q., Silva, C. M., Magalhães-Padilha, D. M., Lima, L. F., Celestino, J. J., Campello, C. C., Silva, J. R., Figueiredo, J. R., and Rodrigues, A. P. (2011). Presence of c-kit mRNA in goat ovaries and improvement of in vitro preantral follicle survival and development with kit ligand. Mol. Cell. Endocrinol. 345, 38–47.
Presence of c-kit mRNA in goat ovaries and improvement of in vitro preantral follicle survival and development with kit ligand.CrossRef | 1:CAS:528:DC%2BC3MXhtFGls7nN&md5=d6009c2a9250b81229a77dd4deddf2b7CAS | 21763396PubMed |

Lu, C. L., Yan, J., Zhi, X., Xia, X., Wang, T. R., Yan, L. Y., Yu, Y., Ding, T., Gao, J. M., Li, R., and Qiao, J. (2015). Basic fibroblast growth factor promotes macaque follicle development in vitro. Reproduction 149, 425–433.
Basic fibroblast growth factor promotes macaque follicle development in vitro.CrossRef | 1:CAS:528:DC%2BC2MXhtVCku7bF&md5=388fb39727909561652132f961f7233dCAS | 25687412PubMed |

Makker, A., Goel, M. M., and Mahdi, A. A. (2014). PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update. J. Mol. Endocrinol. 53, R103–R118.
PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update.CrossRef | 1:CAS:528:DC%2BC2MXmtFKjuw%3D%3D&md5=179bbf3d4b0b26d1e389e5a92e013c49CAS | 25312969PubMed |

Manova, K., Nocka, K., Besmer, P., and Bachvarova, R. F. (1990). Gonadal expression of c-kit encoded at the W locus of the mouse. Development 110, 1057–1069.
| 1:CAS:528:DyaK3MXhs1Wntb4%3D&md5=98095b5858a29a6fea0b049630328023CAS | 1712701PubMed |

Parrott, J. A., and Skinner, M. K. (1999). Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology 140, 4262–4271.
| 1:CAS:528:DyaK1MXlslSru7k%3D&md5=b75c6c76d53feeb6174e47f5b5458ad6CAS | 10465300PubMed |

Penning, L. C., Vrieling, H. E., Brinkhof, B., Riemers, F. M., Rothuizen, J., Rutteman, G. R., and Hazewinkel, H. A. (2007). A validation of 10 feline reference genes for gene expression measurements in snap-frozen tissues. Vet. Immunol. Immunopathol. 120, 212–222.
A validation of 10 feline reference genes for gene expression measurements in snap-frozen tissues.CrossRef | 1:CAS:528:DC%2BD2sXht1agsr%2FI&md5=776e8b3e769b5327fb02532890adcb7aCAS | 17904230PubMed |

Peters, H., and McNatty, K. P. (1980). ‘The Ovary.’ (Granada Press: London.)

Phoophitphong, D., Wangnaitham, S., Srisuwatanasakul, S., and Tummaruk, K. (2012). Use of proliferating cell nuclear antigen (PCNA) immuno-staining technique to determine number and type of follicles in the gilt ovary. Livest. Sci. 150, 425–431.
Use of proliferating cell nuclear antigen (PCNA) immuno-staining technique to determine number and type of follicles in the gilt ovary.CrossRef |

Picton, H. M., Harris, S. E., Muruvi, W., and Chambers, E. L. (2008). The in vitro growth and maturation of follicles. Reproduction 136, 703–715.
The in vitro growth and maturation of follicles.CrossRef | 1:CAS:528:DC%2BD1MXns1CktA%3D%3D&md5=1dccc67e8ac2cfeb619e3343df881ac5CAS | 19074213PubMed |

Pukazhenthi, B. S., Neubauer, K., Jewgenow, K., Howard, J., and Wildt, D. E. (2006). The impact and potential etiology of teratospermia in the domestic cat and its wild relatives. Theriogenology 66, 112–121.
The impact and potential etiology of teratospermia in the domestic cat and its wild relatives.CrossRef | 16644003PubMed |

Reynaud, K., Cortvrindt, R., Smitz, J., and Driancourt, M. A. (2000). Effects of Kit Ligand and anti-Kit antibody on growth of cultured mouse preantral follicles. Mol. Reprod. Dev. 56, 483–494.
Effects of Kit Ligand and anti-Kit antibody on growth of cultured mouse preantral follicles.CrossRef | 1:CAS:528:DC%2BD3cXkslKltbk%3D&md5=189b3231c5e7270e3e29e6bc1ceed12fCAS | 10911398PubMed |

Schmandt, R. E., Broaddus, R., Lu, K. H., Shvartsman, H., Thornton, A., Malpica, A., Sun, C., Bodurka, D. C., and Gershenson, D. M. (2003). Expression of c-ABL, c-KIT, and platelet- derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium. Cancer 98, 758–764.
Expression of c-ABL, c-KIT, and platelet- derived growth factor receptor-beta in ovarian serous carcinoma and normal ovarian surface epithelium.CrossRef | 1:CAS:528:DC%2BD3sXntVWgur0%3D&md5=ac6a9030fb27d06d2ba5a5cc5b869115CAS | 12910520PubMed |

Smitz, J. E., and Cortvrindt, R. G. (2002). The earliest stages of folliculogenesis in vitro. Reproduction 123, 185–202.
The earliest stages of folliculogenesis in vitro.CrossRef | 1:CAS:528:DC%2BD38XhsFChsbo%3D&md5=40fd1e7bb153a1aca25416e36623bc9cCAS | 11866686PubMed |

Songsasen, N., Comizzoli, P., Nagashima, J., Fujihara, M., and Wildt, D. E. (2012). The domestic dog and cat as models for understanding the regulation of ovarian follicle development in vitro. Reprod. Domest. Anim. 47, 13–18.
The domestic dog and cat as models for understanding the regulation of ovarian follicle development in vitro.CrossRef | 23279457PubMed |

Sun, Y., Liu, W. Z., Liu, T., Feng, X., Yang, N., and Zhou, H. F. (2015). Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis. J. Recept. Signal Transduct. Res. 35, 600–604.
Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis.CrossRef | 1:CAS:528:DC%2BC2MXhslCqtbnL&md5=fa684a1365b18f2f5e3e11000bb52e38CAS | 26096166PubMed |

Tiptanavattana, N., Radtanakatikanon, A., Hyttel, P., Holm, H., Buranapraditkun, S., Setthawong, P., Techakumphu, M., and Tharasanit, T. (2015). Determination phase at transition of gonocytes to spermatogonial stem cells improves establishment efficiency of spermatogonial stem cells in domestic cats. J. Reprod. Dev. 61, 581–588.
Determination phase at transition of gonocytes to spermatogonial stem cells improves establishment efficiency of spermatogonial stem cells in domestic cats.CrossRef | 26411537PubMed |

Tisdall, D. J., Fidler, A. E., Smith, P., Quirke, L. D., Stent, V. C., Heath, D. A., and McNatty, K. P. (1999). Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development. J. Reprod. Fertil. 116, 277–291.
Stem cell factor and c-kit gene expression and protein localization in the sheep ovary during fetal development.CrossRef | 1:CAS:528:DyaK1MXkslOltLc%3D&md5=a352f2c7a4d5b7efdbd2d668afee007bCAS | 10615253PubMed |

Trombly, D. J., Woodruff, T. K., and Mayo, K. E. (2009). Roles for transforming growth factor beta superfamily proteins in early folliculogenesis. Semin. Reprod. Med. 27, 14–23.
Roles for transforming growth factor beta superfamily proteins in early folliculogenesis.CrossRef | 1:CAS:528:DC%2BD1MXhvVGntr8%3D&md5=c9c92334f8991cffa5ac8237c0f7cf1dCAS | 19197801PubMed |

van den Hurk, R., and Zhao, J. (2005). Formation of mammalian oocytes and their growth, differentiation, and maturation within ovarian follicles. Theriogenology 63, 1717–1751.
Formation of mammalian oocytes and their growth, differentiation, and maturation within ovarian follicles.CrossRef | 1:CAS:528:DC%2BD2MXitF2js70%3D&md5=e37fa8a32975f95964aa057a9e8ab2c9CAS | 15763114PubMed |

Wright, C. S., Hovatta, O., Margara, R., Trew, G., Winston, R. M., Franks, S., and Hardy, K. (1999). Effects of follicle-stimulating hormone and serum substitution on the in vitro growth of human ovarian follicles. Hum. Reprod. 14, 1555–1562.
Effects of follicle-stimulating hormone and serum substitution on the in vitro growth of human ovarian follicles.CrossRef | 1:CAS:528:DyaK1MXktFGhtL4%3D&md5=3af5f93f0fc48779061c411f3d481044CAS | 10357975PubMed |

Zhang, W., and Liu, H. T. (2002). MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 12, 9–18.
MAPK signal pathways in the regulation of cell proliferation in mammalian cells.CrossRef | 1:CAS:528:DC%2BD38XntVeqtrs%3D&md5=2bd267dee59e05d59dc5d399db31ae2aCAS | 11942415PubMed |



Rent Article (via Deepdyve) Export Citation Cited By (1)

View Altmetrics