Skip to main content

Advertisement

SpringerLink
Log in

Three-Dimensional Cell Culture to Model Epithelia in the Female Reproductive System

  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

In vitro 3-dimensional (3D) cell cultures produce valuable models that mimic 3D tissue organization and function and enhance the understanding of cell/tissue function under normal and pathological situations. Tissue function depends on the interactions between cells and the extracellular matrix; thus, effective 3D cell cultures rely on the use of appropriate extracellular matrix cues. Noticeable progress in 3D cell culture was obtained from studies with epithelial cells from organs of the female reproductive system including the mammary glands, the uterus, and the ovaries. These models show that replicating normal tissue organization in the resting phase is a prerequisite for appropriate physiological and pathological investigations. The authors’ goals are to explain the importance of mimicking detailed aspects of normal epithelial organization and function, such as basoapical polarity, in 3D cell culture and to discuss how effective 3D cell culture models can lead to meaningful applications in reproductive biology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bissell MJ, Hall HG, Parry G. How does the extracellular matrix direct gene expression?J Theor Biol. 1982;99:31–68.

    Article  CAS  PubMed  Google Scholar 

  2. Lelièvre SA, Bissell MJ. Three dimensional cell culture: the importance of context in regulation of function. In: Meyers RA, ed. Encyclopedia of Molecular Cell Biology and Molecular Medicine (EMCBMM). 2nd ed.Vol 14. New York, NY: Wiley; 2005:383–420.

    Google Scholar 

  3. Zhu Y, Maric J, Nilsson M, Brannstrom M, Janson PO, Sundfeldt K. Formation and barrier function of tight junctions in human ovarian surface epithelium. Biol Reprod. 2004;71:53–59.

    Article  CAS  PubMed  Google Scholar 

  4. Auersperg N., Wong AS, Choi KC, Kang SK, Leung PC. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr Rev. 2001;22:255–288.

    CAS  PubMed  Google Scholar 

  5. Rodgers RJ, Irving-Rodgers HF, Russell DL. Extracellular matrix of the developing ovarian follicle. Reproduction. 2003;126:415–424.

    Article  CAS  PubMed  Google Scholar 

  6. Amsterdam A, Plehn-Dujovich D, Suh BS. Structure-function relationships during differentiation of normal and oncogene transformed granulosa cells. Biol Reprod. 1992;46:513–522.

    Article  CAS  PubMed  Google Scholar 

  7. Vollmer G. Endometrial cancer: experimental models useful for studies on molecular aspects of endometrial cancer and carcinogenesis. Endocr RelatCancer. 2003;10:23–42.

    CAS  Google Scholar 

  8. Berkholtz CB, Shea LD, Woodruff TK. Extracellular matrix functions in follicle maturation. Semin Reprod Med. 2006; 24:262–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ferguson JE, Schor AM, Howell A, Ferguson MW. Changes in the extracellular matrix of the normal human breast during the menstrual cycle. Cell Tissue Res. 1992; 268:167–177.

    Article  CAS  PubMed  Google Scholar 

  10. Fata JE, Ho AT, Leco KJ, Moorehead RA, Khokha R. Cellular turnover and extracellular matrix remodeling in female reproductive tissues: functions of metalloproteinases and their inhibitors. Cell Mol Life Sci. 2000;57:77–95.

    Article  CAS  PubMed  Google Scholar 

  11. Salamonsen LA. Tissue injury and repair in the female human reproductive tract. Reproduction. 2003;125:301–311.

    Article  CAS  PubMed  Google Scholar 

  12. Kruk PA, Uitto VJ, Firth JD, Dedhar S, Auersperg N. Reciprocal interactions between human ovarian surface epithelial cells and adjacent extracellular matrix. Exp Cell Res. 1994;215:97–108.

    Article  CAS  PubMed  Google Scholar 

  13. Kreeger PK, Woodruff TK, Shea LD. Murine granulosa cell morphology and function are regulated by a synthetic Arg-Gly-Asp matrix. Mol Cell Endocrinol. 2003; 205:1–10.

    Article  CAS  PubMed  Google Scholar 

  14. Gudjonsson T, Ronnov-Jessen L, Villadsen R, Rank F, Bissell MJ, Petersen OW. Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition. J Cell Sci. 2002;115:39–50.

    CAS  PubMed  Google Scholar 

  15. Arnold JT, Kaufman DG, Seppala M, Lessey BA. Endometrial stromal cells regulate epithelial cell growth in vitro: a new co-culture model. Hum Reprod. 2001;16:836–845.

    Article  CAS  PubMed  Google Scholar 

  16. Plachot C, Lelievre SA. DNA methylation control of tissue polarity and cellular differentiation in the mammary epithelium. Exp Cell Res. 2004; 298:122–132.

    Article  CAS  PubMed  Google Scholar 

  17. Underwood JM, Imbalzano KM, Weaver VM, Fischer AH, Imbalzano AN, Nickerson JA. The ultrastructure of MCF-10A acini. J Cell Physiol. 2006;208:141–148.

    Article  CAS  PubMed  Google Scholar 

  18. Wang F, Weaver VM, Petersen OW, et al. Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proc Natl Acad Sci U S A. 1998;95:14821–14826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Abad PC, Lewis J, Mian IS, et al. NuMA influences higher order chromatin organization in human mammary epithelium. Mol Biol Cell. 2007;18:348–361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Schatz F, Gordon RE, Laufer N, Gurpide E. Culture of human endometrial cells under polarizing conditions. Differentiation. 1990;42:184–190.

    Article  CAS  PubMed  Google Scholar 

  21. Bentin-Ley U, Pedersen B, Lindenberg S, Larsen JF, Hamberger L., Horn T. Isolation and culture of human endometrial cells in a three-dimensional culture system. JReprod Fertil. 1994; 101:327–332.

    Article  CAS  Google Scholar 

  22. Behrens P, Meissner C, Hopfer H, et al. Laminin mediates basement membrane induced differentiation of HEC 1B endometrial adenocarcinoma cells. Biochem Cell Biol. 1996; 74:875–886.

    Article  CAS  PubMed  Google Scholar 

  23. Classen-Linke I, Kusche M, Knauthe R, Beier HM. Establishment of a human endometrial cell culture system and characterization of its polarized hormone responsive epithelial cells. Cell Tissue Res. 1997;287:171–185.

    Article  CAS  PubMed  Google Scholar 

  24. Wong AS, Leung PC. Role of endocrine and growth factors on the ovarian surface epithelium. J Obstet Gynaecol Res. 2007;33:3–16.

    Article  CAS  PubMed  Google Scholar 

  25. Auersperg N, Pan J, Grove BD, et al. E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc Natl Acad Sci U S A. 1999;96: 6249–6254.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pierro E, Nicosia SV, Saunders B, Fultz CB, Nicosia RF, Mancuso S. Influence of growth factors on proliferation and morphogenesis of rabbit ovarian mesothelial cells in vitro. Biol Reprod. 1996; 54:660–669.

    Article  CAS  PubMed  Google Scholar 

  27. Asem EK, Stingley-Salazar SR, Robinson JP, Turek JJ. Identification of some components of basal lamina of avian ovarian follicle. PoultSci. 2000;79:589–601.

    CAS  Google Scholar 

  28. Asem EK, Feng S, Stingley-Salazar SR, Turek JJ, Peter AT, Robinson JP. Basal lamina of avian ovarian follicle: influence on morphology of granulosa cells in-vitro. Comp Biochem Physiol C Toxicol Pharmacol. 2000;125:189–201.

    CAS  PubMed  Google Scholar 

  29. Asem EK, Stingley-Salazar SR, Robinson JP, Turek JJ. Effect of basal lamina on progesterone production by chicken granulosa cells in vitro—influence of follicular development. Comp Biochem Physiol C Toxicol Pharmacol. 2000;125:233–244.

    CAS  PubMed  Google Scholar 

  30. Hwang DH, Kee SH, Kim K, Cheong KS, Yoo YB, Lee BL. Role of reconstituted basement membrane in human granulosa cell culture. Endocr J. 2000;47:177–183.

    Article  CAS  PubMed  Google Scholar 

  31. Schuster MK, Schmierer B, Shkumatava A, Kuchler K. Activin A and follicle-stimulating hormone control tight junctions in avian granulosa cells by regulating occludin expression. Biol Reprod. 2004;70:1493–1499.

    Article  CAS  PubMed  Google Scholar 

  32. Amsterdam A, Josephs R, Lieberman ME, Lindner HR. Organization of intramembrane particles in freeze-cleaved gap junctions of rat graafian rollicles: optical-diffraction analysis. J Cell Sci. 1976;21:93–105.

    CAS  PubMed  Google Scholar 

  33. Anderson E, Lee GY. The polycystic ovarian (PCO) condition: apoptosis and epithelialization of the ovarian antral follicles are aspects of cystogenesis in the dehydroepiandrosterone (DHEA)-treated rat model. Tissue Cell. 1997;29:171–189.

    Article  CAS  PubMed  Google Scholar 

  34. Briand P, Lykkesfeldt AE. An in vitro model of human breast carcinogenesis: epigenetic aspects. Breast Cancer Res Treat. 2001;65:179–187.

    Article  CAS  PubMed  Google Scholar 

  35. Knowles DW, Sudar D, Bator-Kelly C, Bissell MJ, Lelievre SA. Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype. Proc Natl Acad Sci U S A. 2006;103:4445–4450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fournier MV, Martin KJ, Kenny PA, et al. Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer. Cancer Res. 2006;66:7095–7102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Boyd JA, Rinehart CA Jr., Walton LA, Siegal GP, Kaufman DG. Ultrastructural characterization of two new human endometrial carcinoma cell lines and normal human endometrial epithelial cells cultured on extracellular matrix. In Vitro Cell Dev Biol. 1990;26:701–708.

    Article  CAS  PubMed  Google Scholar 

  38. Hopfer H, Rinehart CA Jr., Kaufman DG, Vollmer G. Basement membrane induced differentiation of HEC-1B(L) endometrial adenocarcinoma cells affects both morphology and gene expression. Biochem Cell Biol. 1996;74:165–177.

    Article  CAS  PubMed  Google Scholar 

  39. Saegusa M, Machida D, Okayasu I. Age-dependent differences in tumor cell polarity in endometrial carcinomas. J Cancer Res Clin Oncol. 2002;128:205–213.

    Article  CAS  PubMed  Google Scholar 

  40. Davies BR, Auersperg N, Worsley SD, Ponder BA. Transfection of rat ovarian surface epithelium with erb-B2/neu induces transformed phenotypes in vitro and the tumorigenic phenotype in vivo. Am J Pathol. 1998;152:297–306.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Shih Ie M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am J Pathol. 2004;164:1511–1518.

    Article  PubMed  Google Scholar 

  42. Miller BE, Miller FR, Heppner GH. Factors affecting growth and drug sensitivity of mouse mammary tumor lines in collagen gel cultures. Cancer Res. 1985; 45:4200–4205.

    CAS  PubMed  Google Scholar 

  43. Weaver VM, Lelievre S, Lakins JN, et al. beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell. 2002;2:205–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Kreeger PK, Woodruff TK, Shea LD. Murine granulosa cell morphology and function are regulated by a synthetic Arg-Gly-Asp matrix. Mol Cell Endocrinol. 2003; 205:1–10.

    Article  CAS  PubMed  Google Scholar 

  45. Schindler M, Nur EKA, Ahmed I, et al. Living in three dimensions: 3D nanostructured environments for cell culture and regenerative medicine. Cell Biochem Biophys. 2006;45:215–227.

    Article  CAS  PubMed  Google Scholar 

  46. Kim JH, Yu YS, Kim JH, Kim KW, Min BH. The role of clusterin in in vitro ischemia of human retinal endothelial cells. Curr Eye Res. 2007;32:693–698.

    Article  CAS  PubMed  Google Scholar 

  47. Paszek MJ, Zahir N, Johnson KR, et al. Tensional homeostasis and the malignant phenotype. CancerCell. 2005;8:241–254.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Basic Medical Sciences-Lynn, School of Veterinary Medicine, Purdue University, 625 Harrison Street, West Lafayette, IN, 47907-2026, USA

    Hibret A. Adissu DVM, PhD, Elikplimi K. Asem DVM, PhD & Sophie A. Lelièvre DVM, PhD

Authors
  1. Hibret A. Adissu DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elikplimi K. Asem DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sophie A. Lelièvre DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sophie A. Lelièvre DVM, PhD.

Additional information

Support was provided by the National Institutes of Health (CA112613 to SAL) and an Academic Teaching Fellowship from the Department of Basic Medical Sciences (to HAA). Because of space constraints,we could not cite all the interesting articles related to the topics discussed here.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adissu, H.A., Asem, E.K. & Lelièvre, S.A. Three-Dimensional Cell Culture to Model Epithelia in the Female Reproductive System. Reprod. Sci. 14 (Suppl 8), 11–19 (2007). https://doi.org/10.1177/1933719107310872

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719107310872

Keywords

Search

Navigation