Expression of Keratinocyte Growth Factor in Goat Ovaries and Its Effects on Preantral Follicles Within Cultured Ovarian Cortex


The aims of this study were to evaluate the expression of keratinocyte growth factor (KGF) in goat ovaries and to study its effects on preantral follicle survival and development. The ovaries were used for immunohistochemistry or for in vitro culture for 1 or 7 days with KGF (0, 1, 10, 50, 100, 150, or 200 ng/mL). Noncultured (fresh control) and cultured ovarian slices were processed for histological analysis and transmission electron microscopy (TEM). The results showed that after 7 days of in vitro culture, all treatments had a significant reduction in the percentage of normal follicles compared with the fresh control. After 7 days of culture, the highest KGF concentrations (150 and 200 ng/mL) induced a significant reduction in the percentage of normal follicles compared with the tissues cultured in the absence (α-MEM+ alone) or presence of 1, 10, and 50 ng/mL KGF. Transmission electron microscopy confirmed follicular integrity after 7 days of culture in 1 ng/mL KGF. In addition, compared with the fresh control, the percentage of growing follicles was significantly increased in all treatments after 1 or 7 days of culture. Immunohistochemical analyses showed the expression of KGF in oocytes and granulosa cells in all follicle developmental stages as well as in thecal and stromal cells. In conclusion, this study demonstrated that, at the lowest concentration (1 ng/mL), KGF maintained the ultrastructure of goat preantral follicles cultured in vitro for up to 7 days. Furthermore, the KGF protein was widely distributed in goat ovaries, especially in ovarian follicles.

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  1. 1.

    Hirshfield AN. Development of follicles in the mammalian ovary. Int Rev Cytol. 1991;124:43–101.

  2. 2.

    Adashi EY. Endocrinology of the ovary. Hum Reprod. 1994;9(5):36–51.

  3. 3.

    McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21(2):200–214.

  4. 4.

    Nayudu PL, Fehrenbach A, Kiesel P, Vitt UA, Pancharatna K, Osborn S. Progress toward understanding follicle development in vitro appearances are not deceiving. Arch Med Res. 2001;32(6):587–594.

  5. 5.

    Picton HM, Harris SE, Muruvi W, Chambers EL. The in vitro growth and maturation of follicles. Reproduction. 2008;136(6):703–715.

  6. 6.

    Picton H, Briggs D, Gosden R. The molecular basis of oocyte growth and development. Mol Cell Endocrinol. 1998;145(l-2):27–37.

  7. 7.

    Rubin JS, Bottaro DP, Chedid M, et al. Keratinocyte growth factor. Cell Biol Int. 1995;19(5):399–411.

  8. 8.

    Imagawa W, Cunha GR, Young P, Nandi S. Keratinocyte growth factor and acidic fibroblast growth factor are mitogens for primary cultures of mammary epithelium. Biochem Biophys Res Commun. 1994;204(3):1165–1169.

  9. 9.

    Casey ML, MacDonald PC. Keratinocyte growth factor expression in the mesenchymal cells of human amnion. J Clin Endocrinol Metab. 1997;82(18):3319–3323.

  10. 10.

    Werner S, Smola H, Liao X, et al. The function of KGF in morphogenesis of epithelium and reepithelialization of wounds. Science. 1994;266(5186):819–822.

  11. 11.

    Yi ES, Salgado M, Williams S, et al. Keratinocyte growth factor decreases pulmonary edema, transforming growth factor-b and platelet-derived growth factor-BB expression, and alveolar type II cell loss in bleomycin-induced lung injury. Inflammation. 1998;22(3):315–325.

  12. 12.

    Finch PW, Cunha GR, Rubin JS, Wong J, Ron D. Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions. Dev Dyn. 1995;203(2):223–240.

  13. 13.

    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(2):569–575.

  14. 14.

    Kezele P, Nilsson EE, Skinner MK. Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. Biol Reprod. 2005;73(5):967–973.

  15. 15.

    McGee EA, Chun S-Y, Lai S, He Y-E, Hsueh AJW. Keratinocyte growth factor promotes the survival, growth, and differentiation of preantral ovarian follicles. Fertil Steril. 1999;71(4):732–738.

  16. 16.

    Chaves RN, Martins FS, Saraiva MV, et al. Chilling ovarian fragments during transportation improves viability and growth of goat preantral follicles cultured in vitro. Reprod Fertil Dev. 2008;20(5):640–647.

  17. 17.

    Bruno JB, Celestino JJH, Lima-Verde IB, et al. Expression of vascular endothelial growth factor (VEGF) receptor in goat ovaries and improvement of in vitro caprine preantral follicle survival and growth with VEGF. Reprod Fertil Dev. 2009;21(5):679–687.

  18. 18.

    Donato MAM, Saraiva KLA, Silva AKS, Wanderley MI, Peixoto CA. Follicle development and luteal cell morphology altered by phosphodiesterase-5 inhibitor. Micron. 2009;40(8):845–850.

  19. 19.

    Silva JRV, van den Hurk R, Matos MHT, et al. Influences of FSH and EGF on primordial follicles during in vitro culture of caprine ovarian cortical tissue. Theriogenology. 2004;61(9):1691–1704.

  20. 20.

    Steel RGD, Torrie JH, Dickey DA. Principles and Procedures of Statistics: A Biometrical Approach. 3rd ed. New York, NY: McGraw-Hill; 1997.

  21. 21.

    Salehnia M, Moghadam EA, Velojerdi MR. Ultrastructure of follicles after vitrification of mouse ovarian tissue. Fertil Steril. 2002;78(3):644–645.

  22. 22.

    Wang LH, Mullen SF, Li Y, Zhong JQ, Crister JK, Chen ZJ. Morphological and apoptotic comparison of primordial and primary follicles in cryopreserved human ovarian tissue. Reprod Domest Anim. 2009;44(6):879–883.

  23. 23.

    Magoffin DA. Ovarian theca cell. Int J Biochem Cell Biol. 2005;37(7):1344–1349.

  24. 24.

    Silva JRV, Tharasanit T, Taverne MAM, et al. The activin-follistatin system and in vitro early follicle development in goats. J Endocrinol. 2006;189(1):113–125.

  25. 25.

    Hartshorne GM. In vitro culture of ovarian follicles. Rev Reprod. 1997;2(2):94–104.

  26. 26.

    Chaves RN, Alves AMCV, Duarte ABG, et al. Nerve growth factor promotes the survival of goat preantral follicles cultured in vitro. Cells Tissues Organs. 2010;192(4):272–282.

  27. 27.

    Abir R, Fisch B, Zhang XY, et al. Keratinocyte growth factor and its receptor in human ovaries from fetuses, girls and women. Mol Hum Reprod. 2009;15(2):69–75.

  28. 28.

    Berisha B, Sinowatz F, Schams D. Expression and localization of fibroblast growth factor (FGF) family members during the final growth of bovine ovarian follicles. Mol Reprod Dev. 2004;67(2):162–171.

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Correspondence to L. R. Faustino MS.

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Faustino, L.R., Rossetto, R., Lima, I.M.T. et al. Expression of Keratinocyte Growth Factor in Goat Ovaries and Its Effects on Preantral Follicles Within Cultured Ovarian Cortex. Reprod. Sci. 18, 1222–1229 (2011).

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  • KGF
  • follicle survival
  • folliculogenesis
  • ovary