Validation of the Aging Hen (Gallus gallus domesticus) as an Animal Model for Uterine Leiomyomas1

Abstract

Uterine leiomyomas, or fibroids, are the most frequent gynecological tumors in premenopausal women with as many as 65% of women becoming clinically symptomatic. Uterine fibroids are benign myometrial tumors that produce large quantities of extracellular matrix proteins. Despite its high morbidity, the molecular basis underlying the development of uterine leiomyomas is not well understood. Domestic hens of Gallus gallus domesticus develop oviductal leiomyomas similar to those found in humans. We investigated the natural history of chicken leiomyomas, in vivo expression of protein biomarkers, and in vitro expression of ovarian steroid receptors. Based on the analysis of 263 hens, tumor prevalence, tumor number per hen, and tumor size increased as the hens aged. Immunohistochemistry for alpha-smooth muscle actin (SMA) and desmin confirmed the smooth muscle phenotype of the chicken leiomyomas. Intense collagen expression was detected in these oviductal leiomyomas by Mason's trichrome, and the tumors also showed increased expression of TGFB3 and collagen type I mRNAs. Consistent with human leiomyomas, chicken fibroids displayed increased BCL2 and estrogen (E) and progesterone (P) receptor expression. Chicken leiomyomas were dissociated for in vitro culture. Cells from explants were positive for SMA, desmin, and E and P receptors until the fourth passage. These cells also displayed a response similar to human cells when challenged with halofuginone, an antifibrotic agent. Our findings indicate that the chicken is an excellent complementary model for studies involving the pathophysiology of human uterine leiomyomas.

Leiomyomas of Oviduct and Its Ventral Ligament of Hens: Immunohistochemical Evaluation and the Plasma Concentration Levels of 17 β-Oestradiol and Progesterone

“…Leiomyomas of oviduct and it's VL in hens share several histologic and biological features with human uterine leiomyomas [8][9][10] . Our histochemical and immunohistochemical findings confirm that tumours found on the oviduct and it's VL of hens are derived from smooth muscle cells and there are association between tumorigenesis and ovarian sex steroid hormones.…”

“…administration of oestrogen and progesterone to three weeks old chicks repeated for five weeks was shown to cause leiomyomas of the oviduct VL [1] . Fredrickson et al [8] reported that there were no changes in the plasma concentrations of oestrogen and progesterone in oviduct gland tumours. In addition, such studies on the plasma concentrations of oestrogen and progesterone in leiomyomas of the oviduct VL are limited [5] .…”

“…Although most genital organ leiomyomas in laying hens develop from the oviduct VL, occasional oviduct leiomyomas can also be seen [2] . In humans, uterine leiomyomas are the most common type of reproductive tract tumours in women and leiomyomas of the oviduct in sexually mature domestic hens share important features with human uterine leiomyomas [7][8][9] . The high prevalence and ability to induce leiomyomas of the oviduct VL in hens means that this species could be of interest as a model for the study of similar tumours in mammals as well as women because the remarkable similarities between the ovulatory cyles of women and hens [3,[7][8][9][10][11] .…”

Persistent organic pollutants (POPs) and fibroids: results from the ENDO study

“…We are not aware of any data regarding the interval between exposure and fibroids onset in humans, nor are we aware of sufficient data from relevant animal models (Eker rats or domestic hens). 33,34 Given the long half-life of the POPs evaluated, it is likely that the measured concentrations are reasonable approximations of exposure during the relevant period of exposure. Finally, our results would not retain statistical significance after adjusting for multiple comparisons; however, the exploratory nature of our analysis supports the need for additional studies to evaluate associations between POPs and fibroids.…”

A genome-wide study to identify genes responsible for oviduct development in chickens

“…Because it is more time-consuming and expensive to produce human therapeutic proteins in industrial bioreactors, the demand for the development of transgenic animals as bioreactors is increasing [ 6 ]. The oviduct of transgenic hens may have advantages over mammalian expression systems as a bioreactor to provide potentially new therapeutic proteins [ 7 ], as laying hens over 2 years of age suffer from fibroid tumors that are similar to human fibroid tumors, thereby making them a good animal disease model [ 8 , 9 ].…”