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RESEARCH |
1 Karolinska Institutet, Department of Clinical Science, Intervention and Technology. Karolinska University Hospital, Stockholm, Sweden, 2 Program for Developmental and Reproductive Biology, Biomedicum Helsinki and Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland, 3 Jorvi Hospital, Helsinki University Central Hospital, Espoo, Finland, 4 Infertility Clinic, The Family Federation of Finland, Helsinki, Finland and 5 Department of Reproductive Science and Medicine, Division of Paediatrics, Obstetrics and Gynaecology, Imperial College School of Medicine, Hammersmith Hospital, London, UK
Correspondence should be addressed to O Hovatta, Karolinska Institutet, Department of Clinical Science, Intervention and Technology, Karolinska University Hospital Huddinge, SE 14186 Stockholm, Sweden; Email: Inger.Britt.Carlsson{at}klinvet.ki.se
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Introduction |
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The c-Kit ligand (KL, also called stem cell factor, SCF), a ligand for the c-Kit proto-oncogene receptor tyrosine kinase, is a pluripotent growth factor involved in the differentiation and growth of certain stem cell lineages including hematopoietic stem cells, neuroblasts, melanoblasts and primordial germ cells (PGCs) (Galli et al. 1994). The expression of KL has been detected in granulosa cells in mouse ovaries, while c-Kit receptor is confined to the oocytes and theca interna cells (Manova et al. 1990, 1993, Horie et al. 1991, Keshet et al. 1991, Motro et al. 1991, Motro & Bernstein 1993). In contrast to mice, c-Kit protein and mRNA have been detected in both human oocytes and granulosa cells (Horie et al. 1993, Tanikawa et al. 1998). KL promotes the survival of mouse PGCs in culture independently and in combination with leukemia inhibitory factor (LIF) (Dolci et al. 1991, Godin et al. 1991, Matsui et al. 1991, Pesce et al. 1993). Morita et al.(1999) further showed that KL alone has no inhibitory effect on germ cell apoptosis in cultured prenatal mouse oogonia/oocytes, whereas it was able to promote germ cell survival when administered in combination with LIF. In cultures of fetal mouse ovarian tissue, KL has been found to initiate the growth of oocytes (Klinger & De Felici 2002). KL and c-Kit are also active in fetal mouse and sheep follicular formation (Tisdall et al. 1997, McNatty et al. 2000).
In female mice carrying a distinct mutant allele, Sl pan, that leads to decreased production of KL protein, an almost normal number of germ cells are generated but ovarian follicular growth is arrested at the one-layered granulosa cell stage of the primary follicle (Huang et al. 1993). A similar ovarian phenotype was observed in mice after administering ACK2, an anti-c-Kit antibody that blocks c-Kit/KL receptor–ligand interaction (Yoshida et al. 1997). Moreover, heterozygous mice carrying the mutation Kit (W-lacZ) show alterations in granulosa cell proliferation and oocyte growth in preantral follicles (Reynaud et al. 2001). In cultures of preantral mouse follicles, cytoplasmic maturation of the oocyte and testosterone production by the follicle were improved by addition of KL (50 ng/ml), and blocking the c-Kit receptor by use of an antibody decreased survival of the oocytes (Reynaud et al. 2000). Two oocyte-derived transforming growth factor beta family members, growth differentiation factor 9 (GDF-9) and bone morphogenetic protein 15 (BMP-15, also known as growth differentiation factor 9B) appear to regulate KL expression in a specific manner. GDF-9 suppresses the KL expression in mouse preantral granulosa cells, whereas in bovine antral granulosa cell culture GDF-9 increases KL transcript levels (Joyce et al. 2000, Nilsson & Skinner 2002). BMP-15 stimulates KL expression in rat antral granulosa cells while KL is able to negatively regulate BMP-15 transcripts in a paracrine manner (Otsuka & Shimasaki 2002).
There are differences in rodent and human follicular function, and little is known about the role of KL/c-Kit in early human follicular development. We have previously developed an organ culture method for human primordial, primary and secondary follicles (Hovatta et al. 1997, 1999, Wright et al. 1999, Hreinsson et al. 2002). In this system, follicles are cultured within small slices of ovarian cortical tissue, allowing the maintenance of normal follicular structures and epithelial–stromal interactions. In this study we localized the expression of KL and c-Kit in human ovarian tissue and tested the effects of exogenous KL protein and an antibody against the c-kit receptor, ACK2, on the development and survival of early human ovarian follicles in organ culture.
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Materials and Methods |
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For immunohistochemistry and in situ hybridization analyses, ovarian tissue from six consenting subjects, aged 25–38 years (mean 32), was fixed in Bouin’s solution and embedded in paraffin or directly embedded in OCT cryopreservation solution (TissueTek, Miles, Inc., Elkhart, IN, USA).
Human granulosa-luteal (GL) cell culture
Human GL cells were obtained by follicular aspiration from regularly menstruating women undergoing oocyte retrieval for IVF because of either tubal obstruction or infertility of the spouse. Ovarian stimulation was induced by combining a gonadotropin-releasing hormone analog (Suprecur; Hoechst, Frankfurt am Main, Germany) and human menopausal gonadotropin (Pergonal; Serono Nordic, Vantaa, Finland; or Humegon; Organon, Oss, The Netherlands). Oocyte retrieval was carried out 36–37 h after human chorionic gonadotropin (Profasi; Serono; or Pregnyl; Organon) administration at a total dose of 10 000 IU. The cells obtained the same morning from two to four patients were pooled, enzymatically dispersed, and separated from red blood cells by centrifugation through Ficoll-Paque (Pharmacia, Uppsala, Sweden), as previously described (Eramaa et al. 1993). Thereafter the cells were directly recovered for RNA extraction or plated at a density of 2–5 x 105 cells/well on 35 mm six-well dishes (Costar, Cambridge, MA, USA) and cultured in Dulbecco’s Modified Eagle’s Medium supplemented with 10% fetal calf serum, 2 mM L-glutamine and antibiotics (Gibco) at 37°C in 95% air–5% CO2 humidified environment. Cell culture media were changed every other day. The cells were cultured 6 days before RNA extraction.
Organ cultures
We used an organ culture method that we have described earlier (Hovatta et al. 1997, 1999). Organ cultures were set up in 24-well plates (Nunclon, Roskilde, Denmark) fitted with Millicell CM inserts (12 mm diameter, 0.4 µm pore size; Millipore, Bedford, MA, USA) previously coated with 100 µl of extracellular matrix (Matrigel; Becton Dickinson, MA, USA). Prior to coating, Matrigel was diluted 1:3 with Earle’s balanced salt solution (EBSS; Gibco). Ovarian tissue samples were cut in slices, 0.5–1 mm thick, using a needle and scalpel. The tissue pieces were then either directly fixed for histological analyses (control at 0 days) or placed in the inserts and cultured for 7 or 14 days. Culture medium was EBSS supplemented with either 10% human serum albumin (HSA; Pharmacia Upjohn, Sweden) or inactivated human serum (5%) obtained from women undergoing pituitary desensitization for IVF treatment. Further supplements were FSH (0.11 U/ml; Metrodin or Gonal-F; Serono), and 0.5% antibiotic/antimycotic solution (50 IU/ml penicillin, 50 µg/ml streptomycin sulfate, 0.125 µg/ml amphotericin B; Gibco) at 37 °C in a 95% air–5% CO2 humidified environment. Culture medium (500 µl) was added to each well; three drops (150 µl) were pipetted into the insert with the remainder into the well outside the insert. Every second day, 150 µl culture medium were removed and three drops of fresh medium added to the inserts. Treatment groups in the serum-containing medium were culture medium without (controls) or with recombinant human (rh) SCF at 1, 10 or 100 ng/ml (Sigma) or monoclonal anti-c-kit antibody at 800 ng/ml (ACK2; Sigma), an antagonistic blocker of c-kit function. The diluent of ACK2 was PBS and we diluted it further into culture medium. HSA-containing medium was tested without or with rhSCF (KL) at 10 ng/ml. The cultured pieces were collected for histology and immunohistochemistry.
Histology and follicle counts
The freshly isolated ovarian biopsy material (day 0) or cultured specimens were fixed in Bouin’s solution for 1–2 h, dehydrated in ethanol, embedded in paraffin and serially sectioned at 5 µm thickness. The sections were stained with hematoxylin and eosin. Cells possessing round nuclei along with maintenance of cytoplasmic volume and spherical plasma membranes were considered viable, whereas cells showing eosinophilia of the ooplasm, contraction and clumping of nuclear material as well as wrinkling of the nuclear membrane were considered atretic (Gougeon 1986). From the serial sections, the follicles were counted, their developmental stages were recorded and their diameters were measured at the level of the nuclei of the oocyte by using an ocular micrometer. Care was taken to count each follicle only once as we have also done in our earlier studies (Hreinsson et al. 2002).
Immunohistochemistry
The paraffin sections were incubated at 60 °C for 15 min, serially rehydrated and placed in a water bath. They were incubated for 5 min with peroxidase to block endogenous peroxidase activity and for 30 min with ACK2 (4 µg/ml) diluted in PBS. The sections were then incubated for 30 min with peroxidase-conjugated goat anti-mouse secondary antibody (DAKO EnVision + System; Dako Corporation, Carpinteria, CA, USA). Washing twice with PBS followed each incubation. Finally, the antigenic sites were visualized by using 3,3'-diaminobenzidine (Dako) as a chromogen. Counterstaining was carried out with Erlich’s hematoxylin for 1 min. Immunostaining with PBS + 0.1% BSA (Sigma) and the peroxidase-labeled secondary antibody was used for negative controls. Also antibody against myelin basic protein was used as a negative control. All of the incubations were performed at room temperature unless otherwise specified.
Northern and in situ hybridization
Total RNA from freshly isolated GL cells and cytoplasmic RNA from cultured GL cells were extracted with the guanidine isothiocyanate–cesium chloride method (Chirgwin et al. 1979) and by the modified NP-40 lysis procedure (Ritvos & Eramaa 1991) respectively. Northern blotting was performed as previously described (Laitinen et al. 1997). For filter hybridization reactions we used [
-32P]deoxy-CTP-labeled single- or double-stranded cDNAs. Human c-Kit cDNA was purchased from ATCC (clone no. 59492; ATCC, Manassas, VA, USA). To prepare the cDNA probe, the c-Kit cDNA was first subcloned into pGEM7 vector (Promega, Madison, WI, USA) and cut with EcoRI. The 546 bp (nt 704–1249) single-stranded c-Kit cDNA probe was then synthesized by PCR amplification for 40 cycles using the primer 5'-TAAATCCACTGTGATATCTTA (complementary to the SP6 promoter sequence) (Laitinen et al. 1997). Double-stranded rat glyceraldehyde-6-phosphate dehydrogenase (GAPDH) cDNA (Laitinen et al. 1997) was used as a control for even loading in filter hybridization. GAPDH cDNA was labeled with [-32P]deoxy-CTP and a Prime-a-gene kit (Promega). For in situ hybridization analyses, the [-33P]UTP-labeled antisense cRNA probes were transcribed in vitro from EcoRI-linearized plasmids containing a 905 bp human KL cDNA (Laitinen et al. 1995). In situ RNA analyses were carried out on 9 µm cryostat sections as previously described (Heikinheimo et al. 1997). The slides were dipped in NTB-2 emulsion (Eastman Kodak, New Haven, CT, USA) and exposed for up to 57 days.
Statistical analyses
The data were analyzed using Chi-square and Mann–Whitney U-tests. P < 0.05 was considered significant.
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). To control the technique of hybridization, we also used a probe for an oocyte-specific gene, GDF-9, whose expression is confined to oocytes (Aaltonen et al. 1999).
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). No staining was observed when sections were incubated with only the secondary antibody (Fig. 2B and D).
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, lanes 1 and 2). In cultured GL cells we detected only the shorter transcript (Fig. 3, lane 3). The 5.1 kb transcript represents most likely incompletely processed nuclear transcript, whereas the 4.8 kb transcript is completely processed cytoplasmic RNA and therefore shorter. The absence of longer transcript in cultured GL cells is probably due to the different RNA source (total RNA in freshly isolated GL cells vs cytoplasmic RNA in cultured cells as described in the Materials and Methods section).
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).
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).
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. Similarly to the serum-containing cultures, the proportions of the primary and secondary follicles increased in both KL-containing and control cultures, but there were no significant differences between the KL-containing and control cultures at the two time points (7 and 14 days) studied. There were no differences in the viability, either (data not shown).
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). There were no differences in the mean diameters of the follicles cultured with and without ACK2. The diameters of follicles cultured with ACK2 were 49 µm (79 total follicles) at 7 days and 45 µm (52 total follicles) at 14 days, while the follicles cultured without ACK2 were 47 µm (150 total follicles) at 7 days and 42 µm (71 total follicles) at 14 days of culture.
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). Atresia was already seen in primordial follicles that were cultured in a medium containing ACK2, while it was uncommon in control cultures. The oocytes of primary follicles often had abnormalities in the nucleus after 7 days in cultures containing ACK2. It was observed that some of the granulosa cells were pyknotic or had disappeared leaving only a hole, whereas healthy viable primary follicles were most frequently seen in the control cultures (Fig. 9).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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We showed that KL mRNA is expressed at the primary follicular stage in human ovaries. This is well in line with other studies showing KL expression in granulosa cells in mouse and rat ovaries during early folliculogenesis (Manova et al. 1993, Ismail et al. 1996). We also showed that c-Kit is expressed both in oocytes of early follicles and in granulosa cells of early and antral follicles in human ovaries. These results confirm earlier studies showing expression of c-Kit protein in oocytes and expression of its mRNA in oocytes and preovulatory granulosa cells (Horie et al. 1993, Tanikawa et al. 1998). Although several studies on mice have shown that c-Kit is confined to theca interna cells (Manova et al. 1990, 1993, Horie et al. 1991, Keshet et al. 1991, Motro et al. 1991, Motro & Bernstein 1993), we did not locate its expression in these cells in human ovarian biopsy samples. In this respect, our result is different from that reported by Ito et al.(2001), who used RT-PCR and showed the presence of c-Kit mRNA in human ovarian theca and stroma cells. Our results suggest a species-specific difference in the expression profile of c-Kit.
We have previously developed an extracellular matrix-based method to culture human ovarian follicles in vitro (Hovatta et al. 1997). In these cultures, the structural integrity of the ovarian tissue is maintained and this allows paracrine interactions, which appear necessary, because isolated follicles do not survive or grow as well (Hovatta et al. 1999). Under these culture conditions the follicles grow in diameter and develop to further follicular stages. This is reflected by a 43% decrease in the proportion of primordial follicles during the first 7 days of culture. FSH acts as a survival factor in these cultures (Wright et al. 1999), and insulin and insulin-like growth factors promote the growth and survival of the follicles (Louhio et al. 2000). Furthermore, GDF-9, secreted by the oocyte, is an important factor that promotes the growth and survival of early human follicles in organ culture (Hreinsson et al. 2002). When we added KL to the cultures, there was no clear effect on the development or survival of the follicles. However, increased atresia of early follicles was seen after adding the c-kit blocking antibody to the cultures. The lack of effect of adding KL is probably due to the presence of endogenous KL in the cultures, but the Matrigel could also have been a source of the growth factor. We excluded the possible masking effect of the serum in the culture medium by carrying out also serum-free cultures, with similar results. In cultures of mouse preantral follicles using serum-containing medium, no clear effect was seen, but in serum-free medium KL was mitogenic for granulosa cells (Reynaud et al. 2000). The FSH in our culture medium might also have had a simultaneous effect in preventing apoptosis, masking the effect of ACK2, making further effects difficult to observe (Wright et al. 1999). Also the high rate of spontaneous maturation in vitro may have masked the effect of added KL.
In the rat, KL stimulates the promotion of the developmental stage from primordial to primary follicles (Parrott & Skinner 1999). This was not observed in our cultures, in which we saw an initiation of growth of the primordial follicles within 1 week. Species differences between rodent and human early follicular development may be reflected here, or perhaps the effect of endogenous KL in our cultures. When we added the c-kit blocking antibody to our cultures, we saw similar promotion of the developmental stages as we saw in our control cultures, before the follicles underwent atresia, which is different from the situation in mice and rats (Yoshida et al. 1997, Parrott & Skinner 1999). This indicates a real species difference. A blocking antibody has also been reported to cause a decrease in the survival of mouse oocytes in culture (Reynaud et al. 2000).
We can conclude that c-kit and KL are expressed in human ovaries during early follicular development. Exogenous KL does not improve the survival of follicles in organ culture, but blocking the c-kit receptor induces follicular atresia. The KL/c-kit signaling system is likely to control the survival of human ovarian follicles during early folliculogenesis.
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Footnotes |
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I B Carlsson and M P E Laitinen contributed equally to this paper
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionAcknowledgementsReferences |
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Aaltonen J, Laitinen MP, Vuojolainen K, Jaatinen R, Horelli-Kuitunen N, Seppa L, Louhio H, Tuuri T, Sjoberg J, Butzow R et al. 1999 Human growth differentiation factor 9 (GDF-9) and its novel homolog GDF-9B are expressed in oocytes during early folliculo-genesis. Journal of Clinical Endocrinology and Metabolism 84 2744–2750.
Adashi EY 1991 The Ovarian Life Cycle, pp 181–237. Eds SCC Yen & RB Jaffe. Philadelphia, PA: WB Saunders Co.
Chirgwin JM, Przybyla AE, MacDonald RJ & Rutter WJ 1979 Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18 5294–5299.[CrossRef][Medline]
Dolci S, Williams DE, Ernst MK, Resnick JL, Brannan CI, Lock LF, Lyman SD, Boswell HS & Donovan PJ 1991 Requirement for mast cell growth factor for primordial germ cell survival in culture. Nature 352 809–811.[CrossRef][Medline]
Eramaa M, Heikinheimo K, Tuuri T, Hilden K & Ritvos O 1993 Inhibin/activin subunit mRNA expression in human granulosa-luteal cells. Molecular and Cellular Endocrinology 92 R15–R20.[CrossRef][Web of Science][Medline]
Galli SJ, Zsebo KM & Geissler EN 1994 The kit ligand, stem cell factor. Advances in Immunology 55 1–96.[Web of Science][Medline]
Godin I, Deed R, Cooke J, Zsebo K, Dexter M & Wylie CC 1991 Effects of the steel gene product on mouse primordial germ cells in culture. Nature 352 807–809.[CrossRef][Medline]
Gougeon A 1986 Dynamics of follicular growth in the human: a model from preliminary results. Human Reproduction 1 81–87.[Medline]
Gougeon A 1996 Regulation of ovarian follicular development in primates: facts and hypotheses. Endocrine Reviews 17 121–155.
Heikinheimo M, Ermolaeva M, Bielinska M, Rahman NA, Narita N, Huhtaniemi IT, Tapanainen JS & Wilson DB 1997 Expression and hormonal regulation of transcription factors GATA-4 and GATA-6 in the mouse ovary. Endocrinology 138 3505–3514.
Horie K, Takakura K, Taii S, Narimoto K, Noda Y, Nishikawa S, Nakayama H, Fujita J & Mori T 1991 The expression of c-kit protein during oogenesis and early embryonic development. Biology of Reproduction 45 547–552.[Abstract]
Horie K, Fujita J, Takakura K, Kanzaki H, Suginami H, Iwai M, Nakayama H & Mori T 1993 The expression of c-kit protein in human adult and fetal tissues. Human Reproduction 8 1955–1962.
Hovatta O, Silye R, Abir R, Krausz T & Winston RM 1997 Extracellular matrix improves survival of both stored and fresh human primordial and primary ovarian follicles in long-term culture. Human Reproduction 12 1032–1036.
Hovatta O, Wright C, Krausz T, Hardy K & Winston RM 1999 Human primordial, primary and secondary ovarian follicles in long-term culture: effect of partial isolation. Human Reproduction 14 2519–2524.
Hreinsson JG, Scott JE, Rasmussen C, Swahn ML, Hsueh AJ & Hovatta O 2002 Growth differentiation factor-9 promotes the growth, development, and survival of human ovarian follicles in organ culture. Journal of Clinical Endocrinology and Metabolism 87 316–321.
Huang EJ, Manova K, Packer AI, Sanchez S, Bachvarova RF & Besmer P 1993 The murine steel panda mutation affects kit ligand expression and growth of early ovarian follicles. Developmental Biology 157 100–109.[CrossRef][Web of Science][Medline]
Ismail RS, Okawara Y, Fryer JN & Vanderhyden BC 1996 Hormonal regulation of the ligand for c-kit in the rat ovary and its effects on spontaneous oocyte meiotic maturation. Molecular Reproduction and Development 43 458–469.[CrossRef][Web of Science][Medline]
Ito M, Harada T, Tanikawa M, Fujii A, Shiota G & Terakawa N 2001 Hepatocyte growth factor and stem cell factor involvement in paracrine interplays of theca and granulosa cells in the human ovary. Fertility and Sterility 75 973–979.[CrossRef][Web of Science][Medline]
Joyce IM, Clark AT, Pendola FL & Eppig JJ 2000 Comparison of recombinant growth differentiation factor-9 and oocyte regulation of KIT ligand messenger ribonucleic acid expression in mouse ovarian follicles. Biology of Reproduction 63 1669–1675.
Keshet E, Lyman SD, Williams DE, Anderson DM, Jenkins NA, Copeland NG & Parada LF 1991 Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development. EMBO Journal 10 2425–2435.[Web of Science][Medline]
Klinger FG & De Felici M 2002 In vitro development of growing oocytes from fetal mouse oocytes: stage-specific regulation by stem cell factor and granulosa cells. Developmental Biology 244 85–95.[CrossRef][Web of Science][Medline]
Laitinen M, Rutanen EM & Ritvos O 1995 Expression of c-kit ligand messenger ribonucleic acids in human ovaries and regulation of their steady state levels by gonadotropins in cultured granulosa-luteal cells. Endocrinology 136 4407–4414.[Abstract]
Laitinen M, Ristimaki A, Honkasalo M, Narko K, Paavonen K & Ritvos O 1997 Differential hormonal regulation of vascular endothelial growth factors VEGF, VEGF-B, and VEGF-C messenger ribonucleic acid levels in cultured human granulosa-luteal cells. Endocrinology 138 4748–4756.
Louhio H, Hovatta O, Sjoberg J & Tuuri T 2000 The effects of insulin, and insulin-like growth factors I and II on human ovarian follicles in long-term culture. Molecular Human Reproduction 6 694–698.
Manova K, Nocka K, Besmer P & Bachvarova RF 1990 Gonadal expression of c-kit encoded at the W locus of the mouse. Development 110 1057–1069.
Manova K, Huang EJ, Angeles M, De Leon V, Sanchez S, Pronovost SM, Besmer P & Bachvarova RF 1993 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. Developmental Biology 157 85–99.[CrossRef][Web of Science][Medline]
Matsui Y, Toksoz D, Nishikawa S, Williams D, Zsebo K & Hogan BL 1991 Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture. Nature 353 750–752.[CrossRef][Medline]
McGee EA, Hsu SY, Kaipia A & Hsueh AJ 1998 Cell death and survival during ovarian follicle development. Molecular and Cellular Endocrinology 140 15–18.[CrossRef][Web of Science][Medline]
McNatty KP, Fidler AE, Juengel JL, Quirke LD, Smith PR, Heath DA, Lundy T, O’Connell A & Tisdall DJ 2000 Growth and paracrine factors regulating follicular formation and cellular function. Molecular and Cellular Endocrinology 163 11–20.[CrossRef][Web of Science][Medline]
Morita Y, Manganaro TF, Tao XJ, Martimbeau S, Donahoe PK & Tilly JL 1999 Requirement for phosphatidylinositol-3'-kinase in cytokine-mediated germ cell survival during fetal oogenesis in the mouse. Endocrinology 140 941–949.
Motro B & Bernstein A 1993 Dynamic changes in ovarian c-kit and Steel expression during the estrous reproductive cycle. Developmental Dynamics 197 69–79.[Web of Science][Medline]
Motro B, van der Kooy D, Rossant J, Reith A & Bernstein A 1991 Contiguous patterns of c-kit and steel expression: analysis of mutations at the W and Sl loci. Development 113 1207–1221.[Abstract]
Nilsson EE & Skinner MK 2002 Growth and differentiation factor-9 stimulates progression of early primary but not primordial rat ovarian follicle development. Biology of Reproduction 67 1018–1024.
Otsuka F & Shimasaki S 2002 A negative feedback system between oocyte bone morphogenetic protein 15 and granulosa cell kit ligand: its role in regulating granulosa cell mitosis. PNAS 99 8060–8065.
Parrott JA & Skinner MK 1999 Kit-ligand/stem cell factor induces primordial follicle development and initiates folliculogenesis. Endocrinology 140 4262–4271.
Pesce M, Farrace MG, Piacentini M, Dolci S & De Felici M 1993 Stem cell factor and leukemia inhibitory factor promote primordial germ cell survival by suppressing programmed cell death (apoptosis). Development 118 1089–1094.[Abstract]
Reynaud K, Cortvrindt R, Smitz J & Driancourt MA 2000 Effects of Kit ligand and anti-Kit antibody on growth of cultured mouse preantral follicles. Molecular Reproduction and Development 56 483–494.[CrossRef][Web of Science][Medline]
Reynaud K, Cortvrindt R, Smitz J, Bernex F, Panthier JJ & Driancourt MA 2001 Alterations in ovarian function of mice with reduced amounts of KIT receptor. Reproduction 121 229–237.[Abstract]
Ritvos O & Eramaa M 1991 Adenosine 3',5'-monophosphate and phorbol ester induce transforming growth factor-beta 1 messenger ribonucleic acid levels in choriocarcinoma cells. Endocrinology 129 2240–2245.
Tanikawa M, Harada T, Mitsunari M, Onohara Y, Iwabe T & Terakawa N 1998 Expression of c-kit messenger ribonucleic acid in human oocyte and presence of soluble c-kit in follicular fluid. Journal of Clinical Endocrinology and Metabolism 83 1239–1242.
Tilly JL 1996 Apoptosis and ovarian function. Reviews in Reproduction 1 162–172.[CrossRef]
Tisdall DJ, Quirke LD, Smith P & McNatty KP 1997 Expression of the ovine stem cell factor gene during folliculogenesis in late fetal and adult ovaries. Journal of Molecular Endocrinology 18 127–135.
Wright CS, Hovatta O, Margara R, Trew G, Winston RM, Franks S & Hardy K 1999 Effects of follicle-stimulating hormone and serum substitution on the in-vitro growth of human ovarian follicles. Human Reproduction 14 1555–1562.
Yoshida H, Takakura N, Kataoka H, Kunisada T, Okamura H & Nishikawa SI 1997 Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development. Developmental Biology 184 122–137.[CrossRef][Web of Science][Medline]
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