The high mortality rate due to ovarian cancer is attributed to the lack of an effective early detection method. Due to the non-specificity of symptoms at early stage, most of the ovarian cancer cases are detected at late stages. This makes the access to women with early stage disease problematic and presents a barrier to development and validation of tests for detection of early stage of ovarian cancer in humans. Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Laying hen is the only available animal that develops ovarian cancer spontaneously; however, detail information on ovarian tumor histology is not available. The goal of this study was to determine the histological features of malignant ovarian tumors in laying hens. A total of 155 young and old (1-5 years of age) laying hens (Gallus domesticus) were selected randomly and evaluated gross and microscopically for the presence of ovarian tumors. Histological classification of tumors with their stages and grades were performed with reference to those for humans. Similar to humans, all four types including serous, endometrioid, mucinous and clear cell or mixed carcinomas were observed in hen ovarian tumors. Some early neoplastic as well as putative ovarian lesions were also observed. Similarities in histology, metastasis and stages of hen ovarian cancer to those of humans demonstrate the feasibility of the hen model for additional delineation of the mechanism underlying ovarian carcinogenesis, preclinical testing of new agents for the prevention and therapy of this disease. Keywordsovarian cancer; preclinical model; laying hen; tumor histology Ovarian cancer (OVCA) is a fatal disease of women with the highest mortality rate of all gynecological malignancies. Approximately 70% of women with OVCA die of this disease (1,2). Survival is high in women who present with early stage disease(3,4). The lack of specific symptoms, the relative inaccessibility of the ovaries deep in the pelvis, and the absence of NIH Public Access Author ManuscriptInt J Gynecol Cancer. Author manuscript; available in PMC 2010 May 1. Published in final edited form as:Int J Gynecol Cancer. 2009 May ; 19(4): 531-539. doi:10.1111/IGC.0b013e3181a41613. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript specific marker(s) represent barriers for early detection (5,6). In most cases, OVCA is diagnosed at a late stage(3). Furthermore, our understanding of the early pathogenesis of OVCA has been hindered by the lack of sufficient number of patients with early stage disease (3,4,7). Animal models are used to elucidate disease etiologies and pathogenesis that are difficult to study in humans. Although large domestic mammals including bovine have similar reproductive traits and develop OVCA spontaneously similar to humans, the low incidence rate, multiple pregnancies, longer gestation and lactation period make them an inappropriate model for human OVCA. On the other hand, a number of rodent models, induced or g...

Chorionic gonadotropin (CG) is an early embryo-derived signal that is known to support the corpus luteum. An in vivo baboon model was used to study the direct actions of human CG (hCG) on the endometrium, during the periimplantation period. Endometrial gene expression was analyzed using microarrays. The endometrial biopsies were taken from hCG-treated (n = 5) and control (n = 6) animals on d 10 after ovulation. Class comparison identified 61 genes whose transcript levels differed between control and hCG-treated samples (48 increased, 13 decreased in mean expression level more than 2.5-fold; P < 0.01). Real-time PCR of transcript abundance confirmed up-regulation of several of these, including SerpinA3, matrix metalloproteinase 7, leukemia inhibitory factor (LIF), IL-6, and Complement 3 (P

Spina bifida (SB) patients afflicted with myelomeningocele typically possess a neurogenic urinary bladder and exhibit varying degrees of bladder dysfunction. Although surgical intervention in the form of enterocystoplasty is the current standard of care in which to remedy the neurogenic bladder, it is still a stop-gap measure and is associated with many complications due to the use of bowel as a source of replacement tissue. Contemporary bladder tissue engineering strategies lack the ability to reform bladder smooth muscle, vasculature, and promote peripheral nerve tissue growth when using autologous populations of cells. Within the context of this study, we demonstrate the role of two specific populations of bone marrow (BM) stem/progenitor cells used in combination with a synthetic elastomeric scaffold that provides a unique and alternative means to current bladder regeneration approaches. In vitro differentiation, gene expression, and proliferation are similar among donor mesenchymal stem cells (MSCs), whereas poly(1,8-octanediol-cocitrate) scaffolds seeded with SB BM MSCs perform analogously to control counterparts with regard to bladder smooth muscle wall formation in vivo. SB CD34 + hematopoietic stem/progenitor cells cotransplanted with donor-matched MSCs cause a dramatic increase in tissue vascularization as well as an induction of peripheral nerve growth in grafted areas compared with samples not seeded with hematopoietic stem/progenitor cells. Finally, MSC/CD34 + grafts provided the impetus for rapid urothelium regeneration. Data suggest that autologous BM stem/progenitor cells may be used as alternate, nonpathogenic cell sources for SB patient-specific bladder tissue regeneration in lieu of current enterocystoplasty procedures and have implications for other bladder regenerative therapies.

Using cDNA microarray analysis, we identified SGK1 (serum- and glucocorticoid-regulated kinase 1) as a gene aberrantly expressed in midsecretory endometrium of women with unexplained infertility. SGK1 is a serine/threonine kinase involved primarily in epithelial ion transport and cell survival responses. Real-time quantitative PCR analysis of a larger, independent sample set timed to coincide with the period of uterine receptivity confirmed increased expression of SGK1 transcripts in infertile women compared with fertile controls. We further demonstrate that SGK1 expression is regulated by progesterone in human endometrium in vivo as well as in explant cultures. During the midsecretory phase of the cycle, SGK1 mRNA and protein were predominantly but not exclusively expressed in the luminal epithelium, and expression in this cellular compartment was higher in infertile women. In the stromal compartment, SGK1 expression was largely confined to decidualizing cells adjacent to the luminal epithelium. In primary culture, SGK1 was induced and phosphorylated upon decidualization of endometrial stromal cells in response to 8-bromo-cAMP and progestin treatment. Moreover, overexpression of SGK1 in decidualizing cells enhanced phosphorylation and cytoplasmic translocation of the forkhead transcription factor FOXO1 and inhibited the expression of PRL, a major decidual marker gene. Conversely, knockdown of endogenous SGK1 by small interfering RNA increased nuclear FOXO1 levels and enhanced PRL expression. The observation that SGK1 targets FOXO1 in differentiating human endometrium, together with its distinct temporal and spatial expression pattern and increased expression in infertile patients, suggest a major role for this kinase in early pregnancy events.

Transvaginal sonography can be used to determine ovarian status in hens. It offers the ability to make repeated examinations on the same hen to monitor early changes in the ovary associated with ovarian cancer.