Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The hen as a model of ovarian cancer



The domestic laying hen is the only non-human animal that spontaneously develops ovarian cancer with a high prevalence. Hens ovulate prolifically, and this has made the hen intuitively appealing as a model of this disease in light of epidemiological evidence that ovulation rate is highly correlated with the risk of human ovarian cancer. As in women, ovarian cancer in the hen is age-related and it is also grossly and histologically similar to that in humans. In both women and hens, the cancer metastasizes to similar tissues with an accumulation of ascites fluid. Some aggressive ovarian cancers in women arise from cells in the oviduct; this is intriguing because ovarian cancers in the hen express an oviductal protein that is normally absent in the ovary.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Reproductive tract of a woman compared with the hen reproductive tract.
Figure 2: Hen ovarian tumours.
Figure 3: Subtypes of hen ovarian tumours.


  1. Wey, J. P. & Sellars, T. A. in Cancer Epidemiology, Methods of Molecular Biology (ed. Verma, M.) Vol. 472 413–437 (Humana Press, 2009).

    Google Scholar 

  2. National Cancer Institute. SEER Cancer Statistics Review 1975-2009: Cancer of the ovary. National Cancer Institute (SEER) [online], (2009).

  3. Fathalla, M. F. Incessant ovulation – A factor in ovarian neoplasia? Lancet 2, 163 (1971).

    Article  CAS  PubMed  Google Scholar 

  4. Whittemore, A. S., Harris, R. & Itnyre, J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies. II. Invasive epithelial ovarian cancers in white women. Collaborative Ovarian Cancer Group. Amer. J. Epidemiol. 136, 1184–1203 (1992).

    Article  CAS  Google Scholar 

  5. Ness, R. B. & Cottreau, C. Possible role of ovarian epithelial inflammation in ovarian cancer. J. Natl Cancer Inst. 91, 1459–1467 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Sethi, G., Shanmugan, M. K., Ramachandran, L., Kumar, A. P. & Tergaonkar, V. Multifaceted link between cancer and inflammation. Biosci. Rep. 32, 1–15 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Fredrickson, T. N. Ovarian tumors of the hen. Environ. Health Persp. 73, 35–51 (1987).

    Article  CAS  Google Scholar 

  8. Barnes, M. N. et al. A pilot study of ovarian cancer chemoprevention using medroxyprogesterone acetate in an avian model of spontaneous ovarian carcinogenesis. Gynecol. Oncol. 87, 57–63 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Trevino, L. S., Buckles, E. L. & Johnson, P. A. Oral contraceptives decrease the prevalence of ovarian cancer in the hen. Cancer Prevention Res. 5, 343–349 (2012).

    Article  CAS  Google Scholar 

  10. Urick, M. E., Giles, J. R. & Johnson, P. A. Dietary aspirin decreases the stage of ovarian cancer in the hen. Gynecol. Oncol. 112, 166–170 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Giles, J. R. et al. The restricted ovulatory chicken: a unique animal model for investigating the etiology of ovarian cancer. Int. J. Gynecol. Cancer 20, 738–744 (2010).

    Article  PubMed  Google Scholar 

  12. Carver, D. K. et al. Reduction of ovarian and oviductal cancers in calorie-restricted laying chickens. Cancer Prevention Res. 4, 562–567 (2011).

    Article  CAS  Google Scholar 

  13. Johnson, P. A. & Giles, J. R. Use of genetic strains of chickens in studies of ovarian cancer. Poultry Sci. 85, 246–250 (2006).

    Article  CAS  Google Scholar 

  14. Murdoch, W. J., Van Kirk, E. A. & Alexander, B. M. DNA damages in ovarian surface epithelial cells of ovulatory hens. Exp. Biol. Med. 230, 429–433 (2005).

    Article  CAS  Google Scholar 

  15. Urick, M. E., Giles, J. R. & Johnson, P. A. VEGF expression and the effect of NSAIDS on ascites cell proliferation in the hen model of ovarian cancer. Gynecol. Oncol. 110, 418–424 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Urick, M. E. & Johnson, P. A. Cyclooxygenase 1 and 2 mRNA and protein expression in the Gallus domesticus model of ovarian cancer. Gynecol. Oncol. 103, 673–678 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Hales, B. H. et al. Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus). Endocr. 33, 235–244 (2008).

    Article  CAS  Google Scholar 

  18. Ansenberger, K. et al. Decreased severity of ovarian cancer and increased survival in hens fed a flaxseed-enriched diet for 1 year. Gynecol. Oncol. 117, 341–347 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Auersperg, N., Wong, A. S. T., Chol, K. C., Kang, S. K. & Leung, P. C. K. Ovarian surface epithelium: biology, endocrinology, and pathology. Endocr. Rev. 22, 255–288 (2001).

    CAS  PubMed  Google Scholar 

  20. McCluggage, W. G. Morphological subtypes of ovarian carcinoma: a review with emphasis on new developments and pathogenesis. Pathology 43, 420–432 (2011).

    Article  PubMed  Google Scholar 

  21. Barua, A. et al. Histopathology of ovarian tumors in laying hens: A preclinical model of human ovarian cancer. Int. J. Gynecol. Cancer 19, 531–539 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ansenberger, K. et al. E-cadherin expression in ovarian cancer in the laying hen, Gallus domesticus, compared to human ovarian cancer. Gynecol. Oncol. 113, 362–369 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rodriguez-Burford, C., Barnes, M. N., Berry, W., Partridge, E. E. & Grizzle, W. E. Immunohistochemical expression of molecular markers in an avian model: A potential model for preclinical evalauation of agents for ovarian cancer chemoprevention. Gynecol. Oncol. 81, 373–379 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Zhuge, Y. et al. CYP1B1 expression in ovarian cancer in the laying hen Gallus domesticus. Gynecol. Oncol. 112, 171–178 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Jackson, E., Anderson, K., Ashwell, C., Petitte, J. & Mozdziak, P. E. CA125 expression in spontaneous ovarian adenocarcinomas from laying hens. Gynecol. Oncol. 104, 192–198 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Hakim, A. A. et al. Ovarian adenocarcinomas in the laying hen and women share similar alterations in p53, ras, and HER-2/neu. Cancer Prev. Res. 2, 114–121 (2009).

    Article  CAS  Google Scholar 

  27. Doré, M., Cóté, L. C., Mitchell, A. & Sirois, J. Expression of prostaglandin G/H synthase type 1, but not type 2, in human ovarian adenocarcinomas. J. Histochem. Cytochem. 46, 77–84 (1998).

    Article  PubMed  Google Scholar 

  28. Schildkraut, J. M. et al. Analgesic drug use and risk of ovarian cancer. Epidemiology 17, 104–107 (2006).

    Article  PubMed  Google Scholar 

  29. Harris, R. E., Beebe-Donk, J., Doss, H. & Doss, D. B. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade. Oncol. Rep. 13, 559–583 (2005).

    CAS  PubMed  Google Scholar 

  30. McEntee, M. F. & Whelan, J. Dietary polyunsaturated fatty acids and colorectal neoplasia. Biomed. Pharmacother. 56, 380–387 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Scully, R. E. Ovarian tumors. Amer. J. Pathol. 87, 686–720 (1977).

    CAS  Google Scholar 

  32. Crum, C. P. et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr. Opin. Obstetr. Gynecol. 19, 3–9 (2007).

    Article  Google Scholar 

  33. Kindelberger, D. W. et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am. J. Surg. Pathol. 31, 161–169 (2007).

    Article  PubMed  Google Scholar 

  34. Kim, J. et al. High-grade serous ovarian cancer arises from fallopian tube in a mouse model. Proc. Natl Acad. Sci.USA 109, 3921–3926 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Giles, J. R., Olson, L. M. & Johnson, P. A. Characterization of ovarian surface epithelial cells from the hen: a unique model for ovarian cancer. Exp. Biol. Med. 231, 1718–1725 (2006).

    Article  CAS  Google Scholar 

  36. Barua, A et al. Detection of ovarian tumors in chicken by sonography: a step toward early diagnosis in humans? J. Ultrasound Med. 26, 909–919 (2009).

    Article  Google Scholar 

  37. Barua, A. et al. Contrast-enhanced sonography depicts spontaneous ovarian cancer at early stages in a preclinical animal model. J. Ultrasound Med. 30, 333–345 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Haritani, M. et al. A study on the origin of adenocarcinoma in fowls using immunohistochemical technique. Avian Dis. 28, 1130–1134 (1984).

    Article  CAS  PubMed  Google Scholar 

  39. Giles, J. R., Shivaprasad, H. L. & Johnson, P. A. Ovarian tumor expression of an oviductal protein in the hen: a model for human serous ovarian adenocarcinoma. Gynecol. Oncol. 95, 530–533 (2004).

    Article  CAS  PubMed  Google Scholar 

  40. Trevino, L. S., Giles, J. R., Wang, W., Urick, M. E. & Johnson, P. A. Gene expression profiling reveals differentially expressed genes in ovarian cancer of the hen: support for oviductal origin? Horm. Cancer 1, 177–186 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Kurman, R. J. & Shih, I.-M. The origin & pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am. J. Surg. Pathol. 34, 433–443 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kohler, P. O., Grimley, P. M. & O'Malley, B. W. Protein synthesis: differential stimulation of cell specific proteins in epithelial cells of chick oviduct. Science 160, 86–87 (1968).

    Article  CAS  PubMed  Google Scholar 

  43. O'Malley, B. W., McGuire, W. L. & Korenman, S. G. Estrogen stimulation of synthesis of specific proteins and RNA polymerase activity in the immature chick oviduct. Biochim. Biophys. Acta 145, 204–207 (1967).

    Article  CAS  PubMed  Google Scholar 

  44. Donnez, J., Caasanas-Roux, F., Caprasse, J., Ferin, J. & Thomas, K. Cyclic changes in ciliation, cell height, and mitotic activity in human tubal epithelium during reproductive life. Fertil. Steril. 43, 554–559 (1985).

    Article  CAS  PubMed  Google Scholar 

  45. King, S. M. et al. The impact of ovulation on fallopian tube epithelial cells: evaluating three hypotheses connecting ovulation and serous ovarian cancer. Endocr. Relat. Cancer 18, 627–642 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Hawkridge, A. M. et al. Measuring the intra-individual variability of the plasma proteome in the chicken model of spontaneous ovarian adenocarcinoma. Anal. Bioanal. Chem. 398, 737–749 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Romero, I. L. et al. Effects of oral contraceptives or a gonadotropin-releasing hormone agonist on ovarian carcinogenesis in genetically engineered mice. Cancer Prev. Res. 2, 792–799 (2009).

    Article  CAS  Google Scholar 

  48. Wu, R. et al. Mouse model of human ovarian endometrioid adenocarcinoma based on somatic defects in the Wnt/β-catenin and PI3K/Pten signaling pathways. Cancer Cell 11, 321–333 (2007).

    Article  CAS  PubMed  Google Scholar 

  49. Flesken-Nikitin, A., Choi, K. C., Eng, J. P., Shmidt, E. N. & Nikitin, A. Y. Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 63, 3459–3463 (2003).

    CAS  PubMed  Google Scholar 

  50. Orsulic, S. et al. Induction of ovarian cancer by defined multiple genetic changes in a mouse model system. Cancer Cell 1, 53–62 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Clark-Knowles, K. V., Garson, K., Jonkers, J. & Vanderhyden, B. C. Conditional inactivation of Brca1 in the mouse ovarian surface epithelium results in an increase in preneoplastic changes. Exp. Cell Res. 313, 133–145 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Fumihito, A. et al. One subspecies of the red junglefowl (Gallus gallus gallus) suffices as the matriarchic ancestor of all domestic breeds. Proc. Natl Acad. Sci. USA 91, 12505–12509 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Short, R. V. Breast feeding. Sci. Am. 250, 35–41 (1984).

    Article  CAS  PubMed  Google Scholar 

Download references


The authors are grateful to L. Treviño and M. E. Urick for their intellectual contributions to this project. They also thank the workers at the Cornell University poultry farm for care of the hens.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Patricia A. Johnson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links


Patricia A. Johnson's homepage



An abnormal accumulation of fluid in the abdomen; in the case of ovarian cancer, the fluid often contains free-floating cancer cells that can implant throughout the abdominal cavity.

Corpus luteum

Ovarian structure in mammals that develops from the follicular remnants after ovulation. The corpus luteum characteristically secretes progesterone and is essential for pregnancy.

Inclusion cysts

Fluid-filled structures lined by a single-cell layer of epithelial-like cells. The cysts are found close to the ovarian surface and the cells lining the cavity are thought to be epithelial cells from the ovarian surface that have been trapped deeper inside the ovary during the process of ovulation.

Lactational amennorhea

The normal infertility that occurs after childbirth when a woman is not menstruating and is breastfeeding an infant.


Laying of an egg in which embryonic development occurs outside the body of the mother.

Seasonally anestrous

A period of ovarian inactivity (with no developing follicles), as determined by length of day and thus occurring in certain seasons.

Theca externa layer

The most external cellular layer of the follicle. It is vascularized and produces steroid hormones.

Yolk receptor

A specific receptor on the surface of the avian oocyte that binds the major components of yolk (very low density lipoprotein and vitellogenin) allowing the incorporation of the yolk into the developing oocyte.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Johnson, P., Giles, J. The hen as a model of ovarian cancer. Nat Rev Cancer 13, 432–436 (2013).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer