Abstract
Specific factors that mediate local cell—cell interactions in the ovary related to the initiation and progression of follicle development will be discussed. Recently, several factors produced locally by the primordial follicle have been shown to induce primordial follicle development from a quiescent state to promote follicle development. Kit ligand/stem cell factor (KL/SCF) produced by the immature granulosa cells appears to promote theca cell organization. Basic fibroblast growth factor produced predominately by the oocyte, but by all cells at reduced levels, also was found to induce primordial follicle development similar to KL. It is likely that numerous locally produced factors will mediate cellular interactions and interact between each other to control the induction of primordial follicle development and influence processes such as the onset of puberty and menopause. After follicle development has been induced, theca cells and granulosa cells interact through classical mesenchymal—epithelial type interactions to influence the progression of follicle development. Mesenchymally derived theca cells have been shown to produce transforming growth factor alpha (TGF-α), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and transforming growth factor beta to regulate granulosa cell growth and function. The epithelial granulosa cells have been show to produce KL/SCF that can feed back on the theca cells to regulate theca cell growth and stimulate the production of the theca cell factors (TGF-α, KGF, and HGF). Therefore, a positive feedback loop between the theca cells and granulosa cells appears to exist to promote the dramatic cell growth required during folliculogenesis. Interestingly, hormones such as estrogen and gonadotropins stimulate the expression of these paracrine growth factors. Therefore, the actions of hormones to stimulate follicle development and growth are mediated in part through altering these local cell—cell interactions. In summary, the locally produced paracrine factors that mediate cell—cell interactions involved in primordial follicle development and the progression of follicle development during folliculogenesis are starting to be elucidated.
Article PDF
Avoid common mistakes on your manuscript.
References
Bennett D. Developmental analysis of a mutant with pleiotropic effects in the mouse. J Morphol 1956;98:199–234.
Mintz B, Russell ES. Gene-induced embryological modifications of primordial germ cells in the mouse. J Exp Zool 1957;134:207–37.
McCoshen JA, McCallion DJ. A study of the primordial germ cells during their migratory phase in Steel mutant mice. Experientia 1975;31:589–90.
Manova K, Huang EJ, Angeles M, et al. The expression pattern of the c-kit ligand in gonads of mice supports a role for the c-kit receptor in oocyte growth and in proliferation of spermatogonia. Dev Biol 1993:157:85–99.
Packer AI, Hsu YC, Besmer P, Bachvarova RF. The ligand of the c-kit receptor promotes oocyte growth. Dev Biol 1994;161:194–205.
Yoshida H, Takakura N, Kataoka H, Kunisada T, Okamura H, Nishikawa SI. Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development. Dev Biol 1997;184:122–37.
Chabot B, Stephenson DA, Chapman VM, Besmer P, Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature 1988;335:88–9.
Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell 1988;55:185–92.
Copeland NG, Gilbert DJ, Cho BC, et al. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 1990;63:175–83.
Flanagan JG, Leder P. The kit ligand: A cell surface molecule altered in steel mutant fibroblasts. Cell 1990;63:185–94.
Huang E, Nocka K, Beier DR, et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990;63:225–33.
Zsebo KM, Williams DA, Geissler EN, et al. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990;63:213–24.
Witte ON. Steel locus defines new multipotent growth factor [published erratum appears in Cell 1990 Nov 30;63(5):following 1112]. Cell 1990;63:5–6.
Huang EJ, et al. The murine steel panda mutation affects kit ligand expression and growth of early ovarian follicles. Dev Biol 1993;157:100–9.
Bedell MA, Brannan CI, Evans EP, Copeland NG, Jenkins NA, Donovan PJ. DNA rearrangements located over 100 kb 5’ of the Steel (Sl)-coding region in Steel-panda and Steel-contrasted mice deregulate Sl expression and cause female sterility by disrupting ovarian follicle development. Genes Dev 1995;9:455–70.
Kuroda H, Terada N, Nakayama H, Matsumoto K, Kitamura Y. Infertility due to growth arrest of ovarian follicles in Sl/Slt mice. Dev Biol 1988;126:71–9.
Motro B, Bernstein A. Dynamic changes in ovarian c-kit and steel expression during the estrous reproductive cycle. Dev Dyn 1993;197:69–79.
Manova K, Nocka K, Besmer P, Bachvarova RF. Gonadal expression of c-kit encoded at the W locus of the mouse. Development 1990;110:1057–69.
Horie K, Fujita J, Takakura K, et al. The expression of c-kit protein in human adult and fetal tissues. Hum Reprod 1993;8:1955–62.
Dolci S, Williams DE, Ernst MK, et al. Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature 1991;352:809–11.
Godin I, Deed R, Cooke J, Zsebo K, Dexter M, Wylie CC. Effects of the steel gene product on mouse primordial germ cells in, culture. Nature 1991;352:807–9.
Matsui Y, Toksoz D, Nishikawa S, et al. Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture. Nature 1991;353:750–2.
Ismail RS, Okawara Y, Fryer JN, Vanderhyden BC. Hormonal regulation of the ligand for c-kit in the rat ovary and its effects on spontaneous oocyte meiotic maturation. Mol Reprod Dev 1996;43:458–69.
Parrott JA, Skinner MK. Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology 1999;140:4262–71.
Nishikawa S, Kusakabe M, Yoshinaga K, et al. In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: Two distinct waves of c-kit-dependency during melanocyte development. EMBO J 1991;10:2111–8.
Okura M, Maeda H, Nishikawa S, Mizoguchi M. Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice. J Invest Dermatol 1995;105:322–8.
Yoshinaga K, Nishikawa S, Ogawa M, et al. Role of c-kit in mouse spermatogenesis: Identification of spermatogonia as a specific site of c-kit expression and function. Development 1991;113:689–99.
Oktay K, Schenken RS, Nelson JF. Proliferating cell nuclear antigen marks the initiation of follicular growth in the rat. Biol Reprod 1995;53:295–301.
van Wezel IL, Umapathysivam K, Tilley WD, Rodgers RJ. Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles. Mol Cell Endocrinol 1995;115:133–40.
Yamamoto S, Konishi I, Nanbu K, et al. Immunohistochemical localization of basic fibroblast growth factor (bFGF) during folliculogenesis in the human ovary. Gynecol Endocrinol 1997;11:223–30.
Wordinger RJ, Brun-Zinkernagel AM, Chang IF. Immunohistochemical localization of basic fibroblast growth factor (bFGF) within growing and atretic mouse ovarian follicles. Growth Factors 1993;9:279–89.
Shikone T, Yamoto M, Nakano R. Follicle stimulating hormone induces functional receptors for basic fibroblast growth factor in rat granulosa cells. Endocrinology 1992;131:1063–8.
Wandji SA, Pelletier G, Sirard MA. Ontogeny and cellular localization of 1251-labeled basic fibroblast growth factor and 1251-labeled epidermal growth factor binding sites in ovaries from bovine fetuses and neonatal calves. Biol Reprod 1992;47:807–13.
Lavranos TC, Rodgers HF, Bertoncello I, Rodgers RJ. Anchorage-independant culture of bovine granulosa cells: The effects of basic fibroblast growth factor and dibutyryl cAMP on cell division and differentiation. Exp Cell Res 1994;211:245–51.
Rodgers RJ, Vella CA, F, RH, Scott K, Lavranos TC. Production of extracellular matrix, tibronectin and steroidogenic enzymes, and growth of bovine granulosa cells in anchorage-independent culture. Reprod Fertil Dev 1996;8:249–57.
Gospodarowicz D, Plouet J, Fujii DK. Ovarian germinal epithelial cells respond to basic fibroblast growth factor and express its gene: Implications for early folliculogenesis. Endocrinology 1989;125:1266–76.
Roberts RD, Ellis RCL. Mitogenic effects of fibroblast growth factors on chicken granulosa and theca cells in vitro. Biol Reprod 1999;61:1387–92.
Vernon RK, Spicer LJ. Effects “of basic fibroblast growth factor and heparin on follicle-stimulating hormone-induced steroidogenesis by bovine granulosa cells. J Anim Sci 1994;72:2696–702.
Anderson E, Lee GY. The participation of growth factors in simulating the quiescent, proliferative, and differentiative stages of rat granulosa cells grown in a serum-free medium. Tissue Cell 1993;25:49–72.
Tilly JL, Billig H, Kowalski KI, Hsueh AJ. Epidermal growth factor and basic fibroblast growth factor suppress the spontaneous onset of apoptosis in cultured rat ovarian granulosa cells and follicles by a tyrosine-kinase-dependent mechanism. Mol Endocrinol 1992;6:1942–50.
Neufeld G, Ferrara N, Schweigerer L, Mitchell R, Gospodarowicz D. Bovine granulosa cells produce basic fibroblast growth factor. Endocrinology 1987;121:597–603.
Nilsson E, Parrott JA, Skinner MK. Basic fibroblast growth factor induces primordial follicle development and initiates folliculogenesis. Mol Cell Endocrinol (In Press).
Weidner KM, Hartmann G, Sachs M, Birchmeier W. Properties and functions of scatter factor/hepatocyte growth factor and its receptor c-Met. Am J Respir Cell Mol Biol 1993;8:229–37.
Parrott JA, Vigne JL, Chu BZ, Skinner MK. Mesenchymal-epithelial interactions in the ovarian follicle involve keratinocyte and hepatocyte growth factor production by thecal cells and their action on granulosa cells. Endocrinology 1994;135:569–75.
Matsumoto K, Nakamura T. Emerging multipotent aspects of hepatocyte growth factor. J Biochem 1996;119:591–600.
Rubin JS, Bottaro DP, Chedid M, et al. Keratinocyte growth factor. Cell Biol Int 1995;19:399–411.
Rubin JS, Bottaro DP, Chedid M, et al. Keratinocyte growth factor as a cytokine that mediates mesenchymal-epithelial interaction. Exs 1995;74:191–214.
Parrott JA, Skinner MK. Direct actions of KL on theca cell growth and differentiation during follicle development. Endocrinology 1997;138:3819–27.
Parrott JA, Skinner MK. Developmental and hormonal regulation of hepatocyte growth factor (HGF) expression and action in the ovarian follicle. Biol Reprod 1998;59:553–60.
Parrott JA, Skinner MK. Developmental and hormonal regulation of keratinocyte growth factor (KGF) expression and action in the ovarian follicle. Endocrinology 1997;139:228–35.
Parrott JA, Skinner MK. Theca cell-granulosa cell interactions involve a positive feedback loop among keratinocyte growth factor, hepatocyte growth factor and kit-ligand during ovarian follicular development. Endocrinology 1997;139:2240–5.
Richards JS, Farookhi R. Gonadotrophins and ovarian-follicular growth. Clin Obstet Gynaecol 1978;5:363–73.
Ross GT. Hormones and preantral follicle growth in women. Mayo Clin Proc 1976;51:617–20.
Goldenberg RL, Vaitukaitis JL, Ross GT. Estrogen and follicle stimulation hormone interactions on follicle growth in rats. Endocrinology 1972;90:1492–8.
Rao MC, Midgley AR Jr, Richards JS. Hormonal regulation of ovarian cellular proliferation. Cell 1978;14:71–8.
Richards JS, Midgley AR Jr. Protein hormone action: A key to understanding ovarian follicular and luteal cell development. Biol Reprod 1976;14:82–94.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
This article is published under an open access license. Please check the 'Copyright Information' section either on this page or in the PDF for details of this license and what re-use is permitted. If your intended use exceeds what is permitted by the license or if you are unable to locate the licence and re-use information, please contact the Rights and Permissions team.
About this article
Cite this article
Nilsson, E., Skinner, M.K. Cellular Interactions That Control Primordial Follicle Development and Folliculogenesis. Reprod. Sci. 8 (Suppl 1), S17–S20 (2001). https://doi.org/10.1177/1071557601008001S06
Published:
Issue Date:
DOI: https://doi.org/10.1177/1071557601008001S06