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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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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. open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1

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 | open url image1



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