Journal of Assisted Reproduction and Genetics

, Volume 15, Issue 8, pp 513–520 | Cite as

Immunohistochemical Analysis of Insulin-like Growth Factor–Binding Proteins -1, -2, and -3 in Implantation Sites of the Mouse

  • Mark A. Damario
  • Hung-Ching Liu
  • Carol Ann Mele
  • Marcelo G. Horenstein
  • Zev Rosenwaks


Purpose: Our purpose was to analyze potential interactions between the embryo and the maternal endometrial interface in vivo by analyzing immunolocalization of insulin-like growth factor–binding proteins (IGFBPs) -1, -2, and -3 in implantation sites of the mouse.

Methods: Six-week-old B 6 D 2 F 1 female mice underwent superovulation followed by mating and sacrifice at timed intervals. Formalin-fixed paraffin-embedded tissue was used for avidin–biotin immunocytochemical localization of IGFBPs utilizing standard methodology.

Results: Immunostaining at 1.5 days post coitum revealed light staining in the epithelial glandular cells and faint staining in decidual stroma for both IGFBP-1 and IGFBP-2. At 7.5–10.5 days post coitum, there was moderate–dense immunostaining in the decidualized stromal cells at the implantation site for all three IGFBPs, whereas light immunostaining was seen in nonimplantation site decidua.

Conclusions: Compartmentalization of immunostaining for IGFBP-1, -2, and -3 within decidualized stroma suggests that these proteins may be regulated by trophoblastic and/or embryonic signals.

decidua immunohistochemistry implantation insulin-like growth factor–binding proteins 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rosenfield RG, Lamson G, Pham H, Oh YM, Conover C, DeLeon D, Donovan SM, Ocrant I, Giudice LC: Insulin-like growth factor binding proteins. Rec Progr Horm Res 1991;16:99–159Google Scholar
  2. 2.
    Kelley KM, Oh Y, Gargosky SE, Gucev A, Matsumoto T, Hwa V, Ng L, Simpson DM, Rosenfeld RG: Insulin-like growth factor-binding proteins (IGFBPs) and their regulatory dynamics. Int J Biochem Cell Biol 1996;28:619–637Google Scholar
  3. 3.
    Le Roith D: Insulin-like growth factor receptors and binding proteins. Bailliere's Clin Endocrinol Metab 1996;10:49–73Google Scholar
  4. 4.
    Bell SC, Jackson JA, Ashmore J, Zhu HH, Tseng L: Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells. J Clin Endocrinol Metab 1991;72:1014–1024Google Scholar
  5. 5.
    Giudice LC, Milkowski DA, Fielder PJ, Irwin JC: Characterization of the steroid-dependence of insulin-like growth factor-binding protein-2 synthesis and mRNA expression in cultured human endometrial stromal cells. Hum Reprod 1991;6:632–640Google Scholar
  6. 6.
    Tseng L, Gao J-G, Chen R, Zhu HH, Mazella J, Powell DR: Effect of progestin, antiprogestin, and relaxin on the accumulation of prolactin and insulin-like growth factor-binding protein-1 messenger ribonucleic acid in human endometrial stromal cells. Biol Reprod 1992;47:441–450Google Scholar
  7. 7.
    Giudice LC, Dsupin BA, Irwin JC: Steroid and peptide regulation of insulin-like growth factor-binding proteins secreted by human endometrial stromal cells is dependent on stromal differentiation. J Clin Endocrinol Metab 1992;75:1235–1241Google Scholar
  8. 8.
    Liu H-C, He Z-Y, Mele C, Damario M, Davis O, Rosenwaks Z: Hormonal regulation of expression of messenger RNA encoding insulin-like growth factor binding proteins in human endometrial stromal cells cultured in vitro. Mol Hum Reprod 1997;3:21–26Google Scholar
  9. 9.
    Liu H-C, Mele C, Catz D, Noyes N, Rosenwaks Z: Production of insulin-like growth factor binding proteins (IGFBPs) by human endometrial stromal cells is stimulated by the presence of embryos. J Assist Reprod Genet 1995;12:78–87Google Scholar
  10. 10.
    Kapur S, Tamada H, Dey SK, Andrews GK: Expression of insulin-like growth factor-1 (IGF-1) and its receptor in peri-implantation mouse uterus, and cell-specific regulation of IGF-1 gene expression by estradiol and progesterone. Biol Reprod 1992;46:208–219Google Scholar
  11. 11.
    Rappolee DA, Sturm KS, Behrendtsen O, Schultz GA, Pedersen RA, Werb Z: Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Genes Dev 1992;6:939–952Google Scholar
  12. 12.
    Heyner S, Shah N, Smith RM, Watson AJ, Schultz GA: The role of growth factors in embryo production. Theriogenology 1993;39:151–161Google Scholar
  13. 13.
    Harvey MB, Kaye PL: Insulin-like growth factor-I stimulates growth of mouse preimplantation embryos in vitro. Mol Reprod Dev 1992;31:195–199Google Scholar
  14. 14.
    DeChiara TM, Efstratiadis A, Robertson EJ: A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature 1990;345:78–80Google Scholar
  15. 15.
    Kanai-Azuma M, Kanai Y, Kurohmaru M, Sakai S, Hayashi Y: Insulin-like growth factor (IGF)-I stimulates proliferation and migration of mouse ectoplacental cone cells, while IGF-II transforms them into trophoblastic giant cells in vitro. Biol Reprod 1993;48:252–261Google Scholar
  16. 16.
    Han VKM, Bassett N, Walton J, Challis JRG: The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: Evidence for IGF-IGFBP interactions at the feto-maternal interface. J Clin Endocrinol Metab 1996;81:2680–2693Google Scholar
  17. 17.
    Hahnel A, Schultz GA: Insulin-like growth factor binding proteins are transcribed by preimplantation mouse embryos. Endocrinology 1994;134:1956–1959Google Scholar
  18. 18.
    Markoff E, Henemyre C, Fellows J, Pennington E, Zeitler PS, Cedars MI: Localization of insulin-like growth factor binding protein-4 expression in the mouse uterus during the peri-implantation period. Biol Reprod 1995;53:1103–1109Google Scholar
  19. 19.
    Sadek S, Unterman TG, Bell SC: Epithelial localization of insulin-like growth factor binding protein 1 in the uterus of the rat during pregnancy, deciduoma-bearing pseudopregnancy and hormone treatment. J Reprod Fertil 1994;101:67–75Google Scholar
  20. 20.
    Croze L, Kennedy TG, Schroedter IC, Friesen HG, Murphy LJ: Expression of insulin-like growth factor-I and insulin-like growth factor binding protein-1 in the rat uterus during decidualization. Endocrinology 1996;71:1995–2000Google Scholar
  21. 21.
    Boomsma RA, Mavrogianis PA, Fazleabas AT, Jaffe RC, Verhage HG: Detection of insulin-like growth factor binding protein-1 in cat implantation sites. Biol Reprod 1994;51:392–399Google Scholar
  22. 22.
    Tarantino S, Verhage HG, Fazleabas AT: Regulation of insulin-like growth factor-binding proteins in the baboon (Papio anubis) uterus during early pregnancy. Endocrinology 1992;130:2354–2362Google Scholar
  23. 23.
    Irwin JC, Dsupin BA, Giudice LC: Modulation of cytotrophoblast interaction with fibronectin and endometrial stromal cell cultures by insulin-like growth factor binding protein-1 (IGFBP-1). Presented at the Society for the Study of Reproduction, Sacramento, CA, July 1995Google Scholar
  24. 24.
    Irving JA, Lala PK: Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-β, IGF-II, and IGFBP-1. Exp Cell Res 1995;217:419–429Google Scholar
  25. 25.
    Lee PDK, Conover CA, Powell DR: Regulation and function of insulin-like growth factor binding protein-1. Proc Soc Exp Biol Med 1993;204:4–29Google Scholar
  26. 26.
    Sara VR, Hall K: Insulin-like growth factors and their binding proteins. Physiol Rev 1990;70:591–614Google Scholar
  27. 27.
    Blum WF, Jenne EW, Reppin T, Kietzmann K, Ranke MB, Bierich JR: Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I. Endocrinology 1989;125:766–772Google Scholar
  28. 28.
    Conover CA: Potentiation of insulin-like growth factor (IGF) action by IGF-binding protein-3: Studies of underlying mechanism. Endocrinology 1992;130:3191–3199Google Scholar
  29. 29.
    Koistinen R, Angervo M, Leinonen P, Seppala M: Phosphorylation of insulin-like growth factor-binding protein-1 from different sources. Growth Reg 1993;3:34–37Google Scholar
  30. 30.
    Jones JI, D-Ercole AJ, Camacho-Hubner C, Clemmons DR: Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: Effects on affinity for IGF-1. Proc Natl Acad Sci USA 1991;88:7481–7485Google Scholar

Copyright information

© Plenum Publishing Corporation 1998

Authors and Affiliations

  • Mark A. Damario
    • 1
  • Hung-Ching Liu
    • 1
  • Carol Ann Mele
    • 1
  • Marcelo G. Horenstein
    • 2
  • Zev Rosenwaks
    • 1
  1. 1.Center for Reproductive Medicine and Infertility, Department of Obstetrics and GynecologyCornell University Medical CollegeNew York
  2. 2.Department of PathologyCornell University Medical CollegeNew York

Personalised recommendations