Chronic alcohol (ethanol) consumption has been known to affect the major organs of the body and particularly the liver. However, the effects of chronic ethanol consumption on the female reproductive system remain relatively unstudied. A convenient way to study these effects is by analyzing laboratory mice that have been fed an ethanol diet for an extended period of time and comparing them to control mice. In this study, female mice were separated into control and ethanol fed groups. The mice were placed on their specified diets and observed over the course of six weeks. The mice were fed and weighed daily throughout the duration of the experiment. Once a week, vaginal washes were performed on both groups of mice to determine the stage of the estrous cycle for each mouse. At the end of the six weeks, the mice were sacrificed and the ovaries were harvested and fixed in 4% paraformaldehyde. The ovaries were then paraffin embedded and sectioned. Glass microscope slides were then stained using Hematoxylin and Eosin staining procedures for evaluation using standard light microscopy. The tissue’s morphology, follicle development, presence of corpora lutea, and overall appearance were analyzed. Due to the premature deaths of several mice in first group of ethanol fed mice, the experiment was repeated with three more groups of mice to obtain a better representation of data. The data from the control group was compared to that of the ethanol fed group. The mice that received the ethanol fed diet ceased to cycle and arrested in the diestrous phase of the estrous cycle. Our data indicates that the ovarian follicles within the ethanol fed mice show signs of degeneration in the 4b, 5a, 5b, 6, and 7 levels of development. There are also no notable corpora lutea present within the ovaries of the ethanol fed mice. Our findings indicate that chronic alcohol consumption has deleterious effects on ovarian morphology in mice.

Bibliography: leaves 151-179. / xx, 179 leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines aspects of the distribution of leukocyte subpopulation in human corpus luteum, cytokine determination in human preovulatory follicular fluid, as well as the effects of cytokines on human granulosalutein cells; with the aim of investigating one of the ovarian regulatory systems, which may be controlled by immune cell-derived cytokines. / Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1993

Graduation date: 1995

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 115-136).

With the combination of computer-assisted image analysis and ultrasonographic imaging technology, it has been possible to study and increase the knowledge in different areas of medicine. Studies of ovarian development in female mammals using ultrasonography have shown a relationship between the day in the estrous cycle and the main structures of the ovary.<p>Ultrasound images of bovine ovaries were used to determine whether ultrasound-detected features can automatically determine the phase in the estrous cycle based on a single day's ultrasound examination of the ovaries. Five ultrasound-detected features of the bovine ovaries were used to determine the phase in the estrous cycle: (1) size of the dominant follicle; (2) size of the first subordinate follicle; (3) size of the second subordinate follicle; (4) size of the corpus luteum and (5) number of subordinate follicles with size ≥ 2mm. The collection of ultrasound images used for this study was formed by a group of 45 pairs of ovaries (left and right) which were imaged on day 3, day = 10 and day ≥ 17 of the estrous cycle corresponding to the metestrus, diestrus and proestrus phases respectively.<p>Four different experiments were performed to test the hypothesis. For experiments 1, 2 and 3 the bovine ovaries were classified into three different classes: day 3 of wave 1 (D3W1), day 1 of wave 2 (D1W2) and day 17 or higher (D≥17) that were related to the follicular development of the ovary and the estrous cycle phases as: metestrus, diestrus and proestrus respectively. For experiment 4 the bovine ovaries were classified into four classes: D3W1, D6W1, D1W2 and D≥17. The additional class (D6W1: day 6 of wave 1) was incorporated to represent the early-diestrus phase in the estrous cycle.<p>Two classifiers were implemented for all experiments and their performances compared: a decision tree classifier and a naive Bayes classifier. The decision tree classifier had the best performance with a classification rate of 100% for experiments 1, 2 and 3, giving a rather simple decision tree which used only two features to make a classification: size of the dominant follicle and size of the corpus luteum, suggesting these are key features in distinguishing between phases in the estrous cycle giving the most relevant information. The naive Bayes had a classification rate of 86.36% for experiment 1, 95.55% for experiment 2 and 90% for experiment 3. The results of this study supported the hypothesis that by using ultrasound detected features of bovine ovaries we can determine automatically the stage in the estrous cycle based on a single day's examination.

With the combination of computer-assisted image analysis and ultrasonographic imaging technology, it has been possible to study and increase the knowledge in different areas of medicine. Studies of ovarian development in female mammals using ultrasonography have shown a relationship between the day in the estrous cycle and the main structures of the ovary.<p>Ultrasound images of bovine ovaries were used to determine whether ultrasound-detected features can automatically determine the phase in the estrous cycle based on a single day's ultrasound examination of the ovaries. Five ultrasound-detected features of the bovine ovaries were used to determine the phase in the estrous cycle: (1) size of the dominant follicle; (2) size of the first subordinate follicle; (3) size of the second subordinate follicle; (4) size of the corpus luteum and (5) number of subordinate follicles with size ≥ 2mm. The collection of ultrasound images used for this study was formed by a group of 45 pairs of ovaries (left and right) which were imaged on day 3, day = 10 and day ≥ 17 of the estrous cycle corresponding to the metestrus, diestrus and proestrus phases respectively.<p>Four different experiments were performed to test the hypothesis. For experiments 1, 2 and 3 the bovine ovaries were classified into three different classes: day 3 of wave 1 (D3W1), day 1 of wave 2 (D1W2) and day 17 or higher (D≥17) that were related to the follicular development of the ovary and the estrous cycle phases as: metestrus, diestrus and proestrus respectively. For experiment 4 the bovine ovaries were classified into four classes: D3W1, D6W1, D1W2 and D≥17. The additional class (D6W1: day 6 of wave 1) was incorporated to represent the early-diestrus phase in the estrous cycle.<p>Two classifiers were implemented for all experiments and their performances compared: a decision tree classifier and a naive Bayes classifier. The decision tree classifier had the best performance with a classification rate of 100% for experiments 1, 2 and 3, giving a rather simple decision tree which used only two features to make a classification: size of the dominant follicle and size of the corpus luteum, suggesting these are key features in distinguishing between phases in the estrous cycle giving the most relevant information. The naive Bayes had a classification rate of 86.36% for experiment 1, 95.55% for experiment 2 and 90% for experiment 3. The results of this study supported the hypothesis that by using ultrasound detected features of bovine ovaries we can determine automatically the stage in the estrous cycle based on a single day's examination.

published_or_final_version / Pathology / Master / Master of Medical Sciences

published_or_final_version / Biological Sciences / Master / Master of Philosophy

published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy

Emerging evidences have documented that aberrant expression of FOXM1 is closely associated with human cancers. A recent comprehensive genome analysis has revealed that FOXM1 signaling is one of the major pathways involved in ovarian cancer oncogenesis. However, the regulatory network of FOXM1 in exerting the metastatic phenotypes remains unknown. Therefore, the identification of FOXM1 downstream targets will assist in understanding of its molecular mechanism in ovarian cancer oncogenesis. In this study, by bioinformatics and a series of functional analyses, we identified DLX1 as a novel target of FOXM1. Our results clearly demonstrated that enforced expression of FOXM1 (FOXM1B and FOXM1C) could increase DLX1 in mRNA and protein levels. Conversely, depletion of FOXM1 by Thiostrepton (FOXM1 specific inhibitor) or RNAi knockdown could reduce DLX1 expression. Importantly, we demonstrated that the changes of DLX1 expression were in concomitant with the expression of a positive control gene, Cyclin-D1. Additionally, the luciferase promoter assay further showed that there are two conserved FOXM1 binding sites TFBS1 and TFBS2 which located at -61~-52bp upstream and -737~727bp upstream of the transcription factor binding sites (TSS) of DLX1 promoter respectively. In comparison of two binding sites, the more conserved binding site, TFBS1, seems have higher importance of FOXM1 binding in DLX1 transcriptional activation. Furthermore, our study using immunohistochemical and Q-PCR analyses showed that DLX1 was frequently up-regulated in ovarian cancer samples. Noticeably, clinicopathological analysis revealed that the upregulated DLX1 was significantly associated with not only the overexpressed FOXM1 (P=0.001) but also high grade ovarian cancer (P<0.001). Previous studies have reported that DLX1 is a homeobox transcription factor controlling neuron migration and proliferation in embryogenesis. However, the oncogenic functions of DLX1 are rarely reported. In this study, we revealed that DLX1 could promote ovarian cancer cell proliferation and cell migration which are the main phenomena found in high grade tumors. To the best of our knowledge, this is the first report showing the regulation of FOXM1 on DLX1 and the metastatic functions exerted by DLX1 in ovarian cancer cells. Although ovarian cancer cells are epithelial cell type which is different from neurons, the similar cell functions derived from DLX1 reflecting that both cell types share the similar signaling pathway of DLX1. However, further investigation on the downstream network of DLX1 and the in vivo tumorigenic capacities in ovarian cancer cells are warranted. To conclude, we have identified DLX1 as a novel target of FOXM1 and frequently up-regulated in high grade ovarian cancer. The in vitro tumorigenic assay demonstrated DLX1 could promote cell proliferation and cell migration which are the metastatic properties usually found in high grade ovarian cancer. Therefore, these data highlight the possibilities of using DLX1 as a biomarker and therapeutic target in combating ovarian cancer in the future. / published_or_final_version / Obstetrics and Gynaecology / Master / Master of Philosophy