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1
Tyndall, Victoria. "Androgens and the ovary." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5591.
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Between 10-15% of women suffer from polycystic ovary syndrome (PCOS), making it the most common cause of female infertility. Clinical features of PCOS include high circulating levels of ovarian androgens (T and A4), anovulation and obesity. The aetiology of this reproductive endocrinopathy is likely to be multifactorial, through the interplay of genetics, epigenetics and environmental factors. Primate research into sexual behaviour development noted that fetally androgenised monkeys developed symptoms like those of PCOS. There are now multiple animal models of PCOS using primates, sheep, rats and transgenic mice. The investigations described in this thesis use rodent models to examine the role of androgens in the pathogenesis of female infertility. An attempt to generate a granulosa cell specific androgen receptor knockout mouse model will first be described, followed by several studies into the developmental programming of female Wistar rat infertility and metabolism by steroid hormones. Initial investigations showed that testosterone proprionate (TP) administered to female rats during different windows of fetal and neonatal life alters the reproductive and metabolic axes of the adult animals. Fetal plus neonatal TP exposure led to complete ovarian dysgenesis, while postnatal exposure produced a PCOS-like phenotype. Animals which received TP postnatally were heavier and had an increased proportion of primordial follicles in their ovaries by postnatal day (pnd) 90 of life. Evaluation of this PCOS model showed that neonatally androgenised rats had ovarian follicles with larger antra and a greater ovarian stromal compartment. In addition, these animals were heavier when compared to controls. However, unlike human studies, neonatally androgenised rats showed no differences in circulating gonadotrophin or ovarian androgen levels. Nor did they show any programming effect of neonatal TP upon the theca interna by pnd 90. Further investigations to narrow the windows and dose of TP required to produce a PCOS phenotype showed that TP administered in an early window of neonatal life, between postnatal days (pnd) 1-6 not only led to anovulation, but potentially reprogrammed the hypothalamic-pituitary axis, as there was minimal gonadotrophin response to reduced ovarian negative feedback (inhibin B and estradiol) in these rats. Neonatal TP also affected the rat metabolic axis with adult animals becoming heavier after weaning without any change in food intake. Animals developed mesenteric and retroperitoneal obesity along with insulin resistance (IR). Increased hepatic glucocorticoid turnover and altered adipokine expression were also noted in neonatally androgenised females, possibly contributing to the pathogenesis of obesity. No effect of TP dose upon the severity of infertility or metabolic abnormalities in adult animals was observed. To delineate which features of the rat PCOS model resulted from androgenic, estrogenic or corticosteroid action, a final study used administration of different steroids during the early window of postnatal life: TP, estradiol valerate (EV), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and dexamethasone (DEX). The anovulatory PCO-like phenotype observed with TP was also seen in animals which received EV, but not those which received DHT, DHEA or DEX. TP and EV treatment also resulted in a reduction of ovarian follicle numbers and activated follicle proportions, with an increase in primordial follicle proportions. Although glucose tolerant, animals treated with TP and EV were highly IR. Unlike dexamethasone, DHT and DHEA also produced IR in adult animals, to a lesser extent than TP and EV. Taken collectively, the results described in this thesis demonstrate that the PCOS-like phenotype observed in the neonatally androgenised female rat is likely to be due to the estrogenic actions of testosterone, potentially through as yet unknown epigenetic mechanisms. The programming of the metabolic components described may additionally be due to the actions of androgens. Furthermore, these studies demonstrate a novel estrogenic effect of neonatal steroids upon primordial follicle populations and show that the neonatally androgenised rat may be a rational PCOS model in a poly-ovulatory species.
2
Patterson, Moneka Angilene. "Polycystic Ovary Syndrome Treatment." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/4319.
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Polycystic ovary syndrome (PCOS) is an endocrine system disorder that affects women of reproductive age. If not treated properly, PCOS can lead to infertility. Lack of proper treatment of PCOS may also result in medical complications such as diabetes or heart disease. The rural clinic where this project took place did not have a mandatory guideline for treatment of PCOS; therefore, no standardized method of diagnosis or treatment of PCOS existed. The purpose of this project, guided by the IOWA evidence-based practice model, was to educate providers on the evidence-based guideline for diagnosis and treatment of PCOS outlined by the Endocrine Society Taskforce. The guideline was selected after a comprehensive literature review and was used to develop an educational program that was provided to 5 nurse practitioners, the medical director and staff. A pre-test post-test design was used to determine if the participants understood the content from the guideline that was presented. Results showed that the researcher-developed test administered to participants yielded scores of 74 on the pre-test and increased after the education program with all participants scoring 100 on the post-test. The guideline used for the education was then presented to the clinic for implementation with the assistance of the medical director's support. The project provided an evidence-based guideline for diagnosing and treating PCOS and raised awareness of PCOS among all staff in a rural clinic where many patients with PCOS are treated. Positive social change may result as providers are better prepared to deliver evidence-based care for PCOS and as infertility and complications of untreated PCOS are reduced.
3
Dilaver, Nafi Mehmet. "The role of anti-Mullerian hormone in the ovary : relevance to polycystic ovary syndrome." Thesis, St George's, University of London, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.719152.
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Anti-Mullerian hormone (AMH) is secreted by granulosa cells (GC) in the ovary and is produced in much higher amounts by GCs in women with polycystic ovary syndrome (PCOS). The aim of this project was to examine the role of AMH in the normal ovary and thereby understand the consequences for follicle development of greater concentrations found in women with PCOS. Human granulosa-luteal cells (GLCs), human theca tissue and KGN cells were used to investigate the effect of AMH on GC growth and apoptosis. Furthermore, the relationship between AMH and the essential gonadotrophins of folliculogenesis, i.e. FSH and LH were investigated. AMH signalling was also investigated in GLCs from women with and without PCOS. In addition, the effect of AMH on whole genome expression in GLCs from women with normal ovaries and PCOS was determined. AMH inhibited GC proliferation but did not appear to do this via apoptosis. AMH also had a differential effect on SMAD proteins in normal and PCOS cells. Interestingly, AMH increased inhibitory SMADs 6 & 7 and decreased pSMAD 1/5/8 in PCOS cells compared to basal levels. Finally, AMH had a significant differential effect on the transcriptome profile of cells from women with normal ovaries and PCOS. In summary, a differential effect of AMH in cells from women with normal ovaries and PCOS has been demonstrated, with evidence to speculate that the inhibitory role of AMH in the ovary may be due to an effect on the cell cycle.
4
Wang, Ling Jia. "Cytokines and the human ovary." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phw2458.pdf.
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Bibliography: leaves 151-179. 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.
5
Mannan, Md Abdul. "Steroidogenesis in the developing ovary." Thesis, Royal Veterinary College (University of London), 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522681.
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6
Tomaszczuk-Kossowska, Katarzyna. "Stem cells in the ovary /." [S.l.] : [s.n.], 2009. http://edoc.unibas.ch/diss/DissB_8727.
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7
Morin-Papunen, L. (Laure). "Insulin resistance in polycystic ovary syndrome." Doctoral thesis, University of Oulu, 2000. http://urn.fi/urn:isbn:9514257405.
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Abstract
The polycystic ovary syndrome, described first as the association
of bilateral polycystic ovaries and amenorrhoea, oligomenorrhoea,
hirsutism and obesity, was later shown to be a complex metabolic syndrome.
The first purpose of this study was to investigate the occurrence
of hyperinsulinaemia and the severity of insulin resistance and
glucose tolerance disorders in polycystic ovary syndrome by means of
the oral glucose tolerance test and the euglycaemic hyperinsulinaemic
clamp. The next goal was to investigate whether women with polycystic
ovary syndrome would benefit from insulin-sensitising drugs, and
in particular to compare the effects of metformin and a contraceptive
pill containing ethinyl oestradiol and cyproterone acetate. Altogether,
81 women with polycystic ovary syndrome and 34 healthy control subjects
were involved in the study.
Marked impairment of insulin sensitivity in obese subjects
with polycystic ovary syndrome, including a decrease of both cellular
oxidative and non-oxidative utilisation of glucose, and a slight non-significant
decrease of insulin sensitivity in non-obese subjects was observed.
Both non-obese and obese subjects with polycystic ovary syndrome
exhibited increased abdominal obesity compared with the controls,
confirming the fact that obesity, in particular abdominal obesity,
is an important contributor in the development of insulin resistance
in this syndrome.
Metformin alleviated hyperandrogenism by essentially decreasing
ovarian, but not adrenal androgen secretion. The improvement of
hyperandrogenism and ovarian function seemed to be mediated by the
improvement of hyperinsulinaemia, which resulted itself from subtle
improvements in both hepatic insulin extraction and insulin sensitivity.
Metformin decreased abdominal obesity and the release of free fatty
acids from adipose tissue, and improved ovarian cyclicity and fertility.
The transient decrease in serum leptin levels observed may have
some role in the improvement of ovarian function. The contraceptive
pill significantly improved hyperandrogenism and hirsutism, and
it slightly affected glucose metabolism. Thus, it could be the treatment
of choice in women with hirsutism problems and no fertility hopes.
Metformin could be the drug of choice for women with polycystic
ovary syndrome who wish to conceive. Because of its beneficial metabolic
effects, the value of metformin in reducing the risk of cardiovascular
diseases in polycystic ovary syndrome needs to be further studied.
8
Singh, Jaswant. "Bovine ovary, morphologic and biochemical kinetics." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq24047.pdf.
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9
Cho, Li Wei. "Cardiometabolic aspects of polycystic ovary syndrome." Thesis, University of Hull, 2008. http://hydra.hull.ac.uk/resources/hull:5826.
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Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 6-7% of the population. It is characterised by chronic anovulation and hyperandrogenism with the clinical manifestation of oligomenorrhoea, hirsutism and acne. A ten to twenty fold increased risk for type 2 diabetes in PCOS patients compared to weight matched female control subjects makes the syndrome of high socioeconomic importance. The use of differing diagnostic criteria makes the comparison of studies on PCOS difficult until harmonisation through the Rotterdam consensus in 2004. Despite being removed from the diagnostic criteria by the the Rotterdam consensus, the LH/FSH ratio is still widely used as one of the diagnostic criteria for PCOS. Therefore to determine the usefulness of the LH/FSH ratio in the diagnosis of PCOS, I have conducted a study as described in chapter two and showed that an elevated LH to FSH ratio was as commonly found in normal women as those with PCO, and therefore of no diagnostic value. In January 2004, the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) co-sponsored the Rotterdam polycystic ovary syndrome consensus workshop that published diagnostic guidelines, building on the consensus statement of the National Institutes of Health 1990. The Rotterdam criteria for the diagnosis of PCOS states 2 of the 3 features needs to be present to make the diagnosis, and with the exclusion of other aetiologies (congenital adrenal hyperplasia, androgen-secreting tumors, Gushing's syndrome). These features include (l)Oligo- or anovulation (2)Clinical and/or biochemical signs of hyperandrogenism and (3)Polycystic ovaries (either 12 or more follicles measuring 2-9 mm in diameter, or an ovarian volume of > 10 cm³ ). Following the introduction of this guideline, the diagnosis of PCOS in patients recruited for studies on PCOS have been standardised. However, the current biochemical test for hyperandrogenism in women is still not ideal, due to the variation in the assay at low values. All three of total testosterone, bioavailable testosterone and free androgen index (FAI) are currently used as markers of hyperandrogenism for the diagnosis of PCOS. In chapter three, I evaluated the variability of each of the three markers as well as their use in the diagnosis and monitoring patients with PCOS and found that FAI is a better diagnostic marker for hyperandrogenism in patients with PCOS, but once the diagnosis is made, all three methods are equally good in monitoring disease progression. It has now been recognised that the diagnosis of metabolic syndrome identifies patients at increased risk of developing cardiovascular disease, and attempts have been made to develop the most convenient and useful criteria for the diagnosis of this condition in clinical practice. With the pathogenesis of metabolic syndrome not well understood, central obesity and insulin resistance are acknowledged as important causative factors. Cardiovascular disease studies in PCOS had so far been inconclusive with some suggesting increased cardiac events among women with PCOS whilst other studies suggesting no increase compared with normal cycling women. This may be attributed to small sample size in studies and variation in characteristics of patients recruited as well as surrogate markers used. C-reactive protein (CRP) had been widely used as a marker of inflammation, endothelial dysfunction and risk of cardiovascular disease in general and in patients with PCOS. However, there had not been any studies on the biovailability of this marker as the potential utility of CRP as a marker of cardiovascular risk may be limited by the magnitude of this variability in both health and disease, since there can be substantial overlap between PCOS and control individuals. In chapter four, the biological variation of high sensitivity CRP in women with PCOS were compared to normal menstruating women. I found that while the mean concentration of CRP was higher in individuals with PCOS compared to healthy controls, the intraindividual variation of CRP was similarly large in both groups. Therefore, the potential utility of CRP as a marker of cardiovascular risk may be limited by the magnitude of this variability in both health and disease, since there can be substantial overlap between PCOS and control individuals. PCOS is associated with a high risk of progression to type 2 diabetes (T2DM) and impaired glucose tolerance. A history of T2DM in a first-degree relative appears to define a subset of PCOS subjects with a greater prevalence of insulin secretory defects. However, factors underlying the progression of PCOS to T2DM are unclear and may be due to either an increase in the underlying insulin resistance or the progression of beta cell failure. Chapter five described a comparison study between the insulin resistance and beta cell functions in patients with PCOS to that of diet controlled T2DM. I found that the progression from PCOS to the development of T2DM is unlikely to be due to a further increase in insulin resistance (or variability), but rather the progressive failure of pancreatic beta cells with a decrease in insulin production. Having established the effectiveness in the diagnosis of PCOS and its progression, I went on to establish the effectiveness of individual treatments of PCOS. The treatment of patients with PCOS requires that the specific goal(s) of the therapy be first established. Individual goals may include fertility, treatment for hirsutism and/or acne, achieving a regular menstrual cycle, weight reduction and the prevention of the long term consequences associated with PCOS (type 2 diabetes, dyslipidaemia and possibly cardiovascular disease) - or all of the above. Treatments aimed at modifying the long-term consequences on cardiometabolic aspect of PCOS include weight reduction strategies as well as the use of insulin sensitizers. There is currently insufficient data to suggest the superiority of one treatment over another or the use of these medications for treatment of cardiometabolic risks in patients with PCOS. Endothelial dysfunction had been recognised as an early marker for cardiovascular disease and chapter six compared the changes in endothelial function in women treated with either metformin or pioglitazone. I found that pioglitazone significantly improved endothelial function and hs-CRP whereas metformin did not produce significant improvements. Chapter seven evaluates the effects of orlistat, metformin and pioglitazone on metabolic profile and biological variability of IR in women with PCOS. The results showed that only orlistat reduced both IR and its variability significantly, though all three drugs were effective in reducing hyperandrogenism within the 12 week period of the study. These effects with orlistat were coupled with a significantly reduction in total cholesterol through a reduction in LDL. After conducting the above studies and searching through literatures, I found that studies in cardiometabolic risks in women with PCOS had so far shown conflicting results, and this may be due to the heterogeneity within the group. Chapter eight evaluates this heterogeneity particularly between anovulatory and ovulatory women with PCOS, where all subjects met the Rotterdam criteria. Women with anovulatory PCOS were found to have higher mean and biological variability of IR compared to those having an ovulatory cycle, and both were higher than women without PCOS. This suggests that the subset of patients who ovulate may be better protected against future cardiovascular consequences. In conclusion, this thesis demonstrated that LH/FSH ratio is of no use in the diagnosis of PCOS and that free androgen index appeared to be the best diagnostic marker when compared to total testosterone and bioavailable testosterone.
10
Yasmin, Ephia. "Metabolic aspects of polycystic ovary syndrome." Thesis, University of Leeds, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.545722.
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11
黃虹麗 and Hung-lai Wong. "Gene expression study in ovary cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B4073819X.
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Östman, Josephine. "The fertile ovary transcriptome and proteome." Thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-447785.
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The Human Protein Atlas is an open-source database containing information about protein expression and location in the human cells,tissues and organs. The aim is to map all the proteins in humans using various biotechnology techniques such as antibody-based imaging, andRNA sequencing etc. Based on previous transcriptome analysis, 173 genes were shown to have an elevated expression in ovary compared to all other major tissue types in the human body. There is however no information regarding the expression in ovary during the reproductive years versus the post-menopausal years. In this thesis, the gene expression in ovaries of women in reproductive age was compared with women in post-menopausal age. 509 genes were found to have an at least 2-fold higher mean value RNA expression in the reproductive age group. 14 of these genes were analyzed further with antibody staining and multiplex immunofluorescence staining to localize the corresponding proteins. The results show that these genes are expressed in a variety of structures in the ovarian tissue, such as the oocyte, the granulosa cells and the corpus luteum. This thesis has demonstrated how data analysis can be used to find genes important for the ovary of women in reproductive age and in the future, this could aid research in female fertility.
13
Wong, Hung-lai. "Gene expression study in ovary cancer." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B4073819X.
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Baker, Elizabeth. "Illness Perceptions of Polycystic Ovary Syndrome." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5176.
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Polycystic ovary syndrome (PCOS) is a chronic illness that affects approximately five million premenopausal women in the United States and is associated with significant cosmetic, reproductive, metabolic, and psychological consequences. Despite its prevalence, few studies have explored the lived experiences and illness perceptions of women living with PCOS. Identifying illness perceptions of women living with (WLW) PCOS is important, because mounting research suggests that a person's perceptions of their chronic illness and its management determine that person's coping behaviors (e.g., adherence, self-management) and, consequently, illness outcomes.
In this dissertation, the Common Sense Model (CSM) is used as a framework to identify the illness perceptions of PCOS held by WLW the syndrome. As such, this dissertation is the first to test the ecological validity of the CSM in a population of women diagnosed with PCOS. In addition, the relationship between illness perceptions and (1) infertility, a common symptom of the syndrome, and (2) health-related quality of life (HRQoL) is explored. Lastly, this study makes a novel contribution to the literature by describing one of the first samples of WLW PCOS recruited through a social networking site. This includes a discussion of the participant's demographic information, fertility experiences, and HRQoL.
This is a two-phase mixed methods study. Phase one consisted of an online quantitative survey capturing data on 376 participants' demographic information and medical history. Data were also collected on each participant's HRQoL using the SF-36, a generic, well-validated measure of the phenomenon. Of the 376 survey participants, 34 were interviewed via phone or video chat in the fall 2013 and spring 2014 semesters. Quantitative data were downloaded from Qualtrics® and analyzed using SAS statistical software version 9.3. In this analysis, descriptive statistics were generated to describe sample characteristics and SF-36 domain scores were calculated for each participant. In the qualitative analysis, data were analyzed through a series of sorting techniques and transcripts were imported into NVivo 10 and subjected to content analysis.
The mean age of survey participants was 31.8 years (SD=5.8). Respondents were primarily non-Hispanic (92.5%), white (88.3%), straight (94.4%), and married (73.4%) with a college education (64.1%). On average, participants reported living with PCOS for 7.6 years (SD=6.1). Approximately half of the sample reported having biological children (47.9%) and currently trying to conceive (42.1%), and most participants reported a history of infertility (70.7%). In addition, almost half of the total sample reported heights and weights that placed them in the morbidly obese category (BMI>35). Lastly, a history of depression (63.6%) and anxiety (68.6%) was common among participants.
Few survey participants reported their general health as being excellent (2.6%) or very good (27.4%). Similarly, women reported the lowest levels of functioning on the dimension of vitality, meaning that, in general, women reported feeling tired and being low in energy. Conversely, women reported the highest scores on the dimensions of physical functioning and role limitations due to physical health, meaning that, in general, women did not report that their health limited their physical abilities or caused problems with work or other daily activities.
Interview findings suggest that WLW PCOS generally have illness perceptions of the syndrome that are consistent with the domains identified in the CSM. In addition, it was found that, in relation to their illness cognitions, WLW PCOS described the extent to which they felt they had a comprehensive understanding of the syndrome, a phenomenon labeled illness coherence. Similarly, participants identified PCOS as a common condition (i.e. labeled perceived prevalence). Lastly, a number of relationships were identified between illness perceptions and (1) infertility status and (2) HRQoL scores.
Overall, this dissertation identifies a number of implications for patient education, provider education, clinical practice, and policy improvements. Examples include addressing (1) unmet information needs, (2) significant psychological morbidity and unmet mental health needs, (3) breastfeeding challenges and need for breastfeeding support, (4) poor quality of care and low patient satisfaction, and (5) limited access to care - all among women living with PCOS.
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Lindholm, Åsa Maria. "Metabolic Aspects in the Polycystic Ovary Syndrome." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-120235.
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Vanky, Eszter. "Polycystic ovary syndrome - Metformin treatment in pregnancy." Doctoral thesis, Norwegian University of Science and Technology, Faculty of Medicine, 2005. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-688.
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Lindholm, Åsa Maria. "Metabolic Aspects in the Polycystic Ovary Syndrome." Doctoral thesis, Uppsala universitet, Institutionen för kvinnors och barns hälsa, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-120235.
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Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of childbearing age and is associated with a number of metabolic disturbances. It has been hypothesised these women carry an increased risk of developing cardiovascular diseases (CVD) with advancing age. The first aim of this thesis was to establish the prevalence of PCOS-related symptoms in Northern Sweden. The Northern part of the WHO MONICA project was used for this purpose. Based on self-reported menstrual disturbances and hirsutism together with biochemical analyses of free androgen index, the estimated prevalence of PCOS in Northern Sweden was 4.8%, which corresponded with previous prevalence studies. Disturbances in the fibrinolytic system are predictors of future cardiovascular events and measurements of plasminogen activator inhibitor 1 (PAI-1) activity and tissue plasminogen activator (tPA) mass concentration may be used to assess fibrinolytic activity in women with PCOS. From the findings, over-weight women with PCOS had impaired fibrinolysis, especially if they displayed objective biochemical markers of hyperandrogenism. Conversely, lean women with PCOS, displayed no signs of disturbed fibrinolysis. The adipose tissue is an active endocrine organ that produces and releases hormones, pro- and anti-inflammatory cytokines, and chemoattractant cytokines. Proinflammatory molecules produced by adipose tissue can be active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. The findings suggested being overweight, rather than the PCOS diagnosis per se, was the main explanatory variable for elevated adipose tissue inflammation in PCOS patients. Weight reduction is the primary target for intervention in overweight and obese women with PCOS. When this thesis was planned, no placebo-controlled trials on anti-obesity drugs in women with PCOS had been conducted. Sibutramine in combination with lifestyle intervention resulted in significant weight reduction in overweight women with PCOS. In addition to the weight loss, sibutramine appeared to have a beneficial effect on metabolic and cardiovascular risk factors.
18
Gharani, Neda. "The molecular genetics of polycystic ovary syndrome." Thesis, Imperial College London, 2000. http://hdl.handle.net/10044/1/8841.
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Sluijmer, Alexander Victor. "The postmenopausal ovary functional and morphological aspects /." [Maastricht : Maastricht : Universiteit Maastricht] ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=6841.
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Lannagan, Tamsin R. M. "Role of TrkB in neonatal ovary development." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4147.
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The signalling cascade induced by the binding of neurotrophins (NGF, BDNF, NT3 and NT4) to their high-affinity tyrosine kinase receptors (TrkA, B and C) is well documented to be important for neuronal cell survival, proliferation and differentiation. Evidence has accumulated demonstrating the importance of these signalling pathways in nonneuronal tissues, including the ovary where all neurotrophins and their receptors are expressed. In the mouse, effects on ovulation have been demonstrated but the role of Trk signalling in neonatal ovary development is less clear. Previous work had found that TrkB expression is upregulated at the time of follicle formation in the mouse and transgenic mice null for the TrkB receptor demonstrate significant loss of oocytes neonatally (TrkB knockouts, KO, die shortly after birth). This thesis examines the phenotype of the TrkB KO using morphological, histological and surgical techniques with the aim being to further investigate the role of TrkB signalling in oocyte survival, and to contribute to our understanding of neonatal ovary development. The main questions addressed are: 1) what developmental defects are occurring on a morphological level that result in the phenotype of the TrkB KO; 2) can these defects be quantified; and 3) what are the longterm survival prospects for TrkB KO oocytes. Morphological assessment revealed that TrkB KO ovaries exhibit poorer follicle health than their Controls and this was confirmed by assessment of basement membrane (BM) composition. TrkB KO brain and kidney were also assessed and found to have similarly affected BM. It is well known that cells require contact with the BM to maintain survival, thus it is postulated that TrkB signalling contributes to oocyte survival through regulation of the BM. Due to the postnatal lethality of the mutation, TrkB KO ovaries were transplanted to ascertain long-term oocyte survival. Unexpectedly it was found that TrkB KO oocytes are able to survive and follicles grow as well as they do in the Control transplants. Consequently, the in vivo effect has to be indirect. It is known that oocytes in the neonatal ovary undergo an increased rate of cell death but it is not known how the cell debris is removed. A novel observation of a neonatal ovarian immune response has been made in this thesis and is postulated to be a physiological mechanism for cell debris clearance. In conclusion, this thesis has demonstrated that signalling through TrkB has an effect on regulating BM in the ovary and other organs, but that surprisingly it has an indirect effect on oocyte survival.
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Atiomo, William Usinode. "Polycystic ovary syndrome coagulation and metabolic studies." Thesis, University of Plymouth, 1998. http://hdl.handle.net/10026.1/2828.
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The polycystic ovary syndrome (PCOS) is a heterogeneous disorder in women characterised by chronic ovulatory failure, hyperandrogenaemia, and insulin resistance. Some women are completely asymptomatic and others present with extreme menstrual disturbance, severe hirsutism, infertility and recurrent miscarriage. The pathophysiology of PCOS is not completely understood, but it is thought that insulin resistance plays a central role. In normal subjects, non-diabetic obese patients and patients with non-insulin dependent diabetes, insulin resistance is associated with elevated plasminogen activator inhibitor-1 (PAI-1) levels. PAI-1 is a glycoprotein, which inhibits the formation of plasmin (a proteolytic enzyme). Plasmin aids fibrinolysis and extracellular proteolysis. High PAI-1 and low plasmin levels increase the risk of thrombosis and impair extracellular proteolysis required in ovarian follicle growth, ovulation and embryo implantation. This study was designed to determine whether elevated plasminogen activator inhibitor-1 (PAI-1) was associated with the insulin resistance present in PCOS, investigate its possible role in the causation of anovulation and recurrent pregnancy loss in these women and ascertain whether it was an additional thrombotic risk factor so that clinicians and patients could take appropriate measures to reduce this risk In a pilot study, systemic PAI-1 activity was significantly elevated in oligomenorrhoiec women with PCOS. A larger study supported these findings, but demonstrated that obesity was a significant confounding factor, as the increase in PAI-1activity disappeared when standardised for weight. Activated Protein-C (APC) resistance was subsequently tested in these women because of the unexpected finding of an increased prevalence of a positive family history of thrombosis in women with PCOS compared with controls, but there was no increase in the prevalence of APC-resistance in PCOS. In another project, the cellular distribution of PAI-1 protein in human ovaries was described for the first time using immunohistochemistry. It was localised to the granulosa and theca cell compartments in both polycystic and normal ovaries, however there was no significant difference in the intensity of PAI-l staining between both groups on image analysis. PAI-1 messenger RNA expression was also evaluated in these biopsies by in-situ hybridisation, but no signal was detected suggesting that there was either a low overall RNA preservation in the tissues, or an insufficient sensitivity of the cocktail of oligonucleotide probes used. This study did not support the hypothesis that elevated PAI-1 was a feature of PCOS, however the in-situ location of PAI-1 protein was demonstrated for the first time in the human ovary and consistent with a previously suspected role in ovulation. The results did not support a role for PAI-1 in anovulation, recurrent miscarriage or increased thrombosis in PCOS.
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Chavez-Ross, Maria Alexandra. "Follicle selection dynamics in the mammalian ovary." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391766.
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Onions, Vicki Jean. "Development of whole ovary cryopreservation in sheep." Thesis, Nottingham Trent University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.444616.
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Syddall, Katie Louise. "Directed evolution of Chinese Hamster Ovary cells." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/13836/.
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Morgan, Stephanie. "How do chemotherapeutic agents damage the ovary?" Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9543.
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Chemotherapy treatment in premenopausal women has been linked to premature ovarian failure (POF), and hence infertility, through ovarian follicle loss. The exact mechanisms that lie behind this loss are unclear and so the action of two commonly used chemotherapeutic agents were compared here. Cisplatin is a DNA cross-linking agent commonly used in the treatment of ovarian, lung and bladder cancers, while the anthracycline doxorubicin is commonly used to treat leukaemia and breast cancer. Neonatal mouse ovaries were cultured in vitro and exposed to cisplatin or doxorubicin in order to determine their effects on primordial and early growing follicles. Both drugs caused a dose dependant follicle loss but targeted different cell types. Cisplatin caused a significant increase in follicles with unhealthy oocytes; furthermore primary stage follicles were the follicle class most affected (up to 98% classified as unhealthy compared with 13% in control, p<0.001). In contrast, doxorubicin caused a significant increase in follicles with unhealthy granulosa cells and affected all follicle stages present. When the mechanism of cell death was further investigated, apoptosis was the main pathway through which these drugs cause ovarian cell death. Doxorubicin in particular caused a significant increase in apoptosis of ovarian somatic cells including the granulosa cells and stroma. Imatinib mesylate, a tyrosine kinase inhibitor which is also used as a chemotherapeutic agent, has been implicated as a potential therapy to block the ovotoxic effects of cisplatin. Results here confirm this finding (29% of follicles classified as unhealthy in the cisplatin only group compared to 8% in the cisplatin and imatinib co-treatment group, p<0.001) and found further, that imatinib was unable to protect against doxorubicin-induced damage (28% of follicles classified as unhealthy in the doxorubicin treated group compared to 19% in the doxorubicin and imatinib cotreatment group). Imatinib treatment alone in newborn ovaries caused a significant increase in the number of follicles present at the end of culture compared to control (402±43 in the imatinib group compared to 188±34 in control, p<0.001), which is likely due to an effect on follicle formation. In conclusion, the work presented in this thesis demonstrates drug specific actions of cisplatin and doxorubicin on the mouse ovary. This suggests that any therapy designed to confer ovarian protection in the future may have to be tailored to be drug specific.
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Murdoch, Alison Pamela. "Hypothalamic-pituitary relationships in polycystic ovary syndrome." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/19176.
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Hresko, M. D. "Polycystic ovary syndrome in the older women." Thesis, БДМУ, 2020. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/17619.
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Sahota, Sukhwinder K. "The genetic basis of polycystic ovary syndrome." Thesis, University of Aberdeen, 2000. http://digitool.abdn.ac.uk/R?func=search-advanced-go&find_code1=WSN&request1=AAIU134381.
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Polycystic ovary syndrome (PCOS) affects up to 10% of women of a reproductive age and is a major cause of infertility. It is characterised by polycystic ovaries, hyperandrogenism and chronic anovulation. The disorder is genetically inherited and possibly of polygenic nature. Two methods were employed in the investigation of the genetic basis of PCOS: DD RT-PCR and mutation screening for association based studies. Application of DD RT-PCR on ovarian granulosa cells cells from affected and control women identified twenty-three differentially expressed sequences (B1-23). Of these, B4 was confirmed to be differentially expressed in A PCOS patient by competitive RT-PCR. Similarity searching identified the B4 sequence as the PHEX gene (99% homology). The corresponding PHEX protein is postulated to act as an endopeptidase in phosphate regulation. Its role in the ovary of PCOS patients remains to be elucidated. An association based study indicated reduced risk of PCOS associated with the AA genotype (OR=0.04; P<0.05) of the FSHR G2039A polymorphism in antenatal controls. No difference was seen between PCOS and blood donor control individuals. The 2039A allele confers a novel glycosylation site in the peptide sequence and this may effect processing of the FSHR protein in the endoplasmic reticulum. In addition, a reduced risk of PCOS was associated with the -1944CC genotype (OD=0.3) of the -1994 novel polymorphic site in CYP11a in blood donor controls. These findings suggest that a number of genetic factors may be involved in pathogenesis of PCOS. Their identification will open the potential for direct treatment of the symptoms associated with the disorder, especially infertility, and prophylactic management of those patients most at risk from cardiac disease or NIDDM.
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Kim, Jong G. "Cytokines and Ovulation in the Mouse Ovary." Digital Commons @ East Tennessee State University, 1994. https://dc.etsu.edu/etd/2711.
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Ovulation has been hypothesized as an inflammatory process. Interleukin(IL)-1$\alpha$, IL-1$\beta$ and tumor necrosis factor(TNF)-$\alpha$ are potent cytokines produced from macrophages and various other cell types, and are pivotal components of inflammation. Although previous studies have investigated cytokine activities in the reproductive system, there is little information on their precise localization and activities during the periovulatory period. To investigate the role of cytokines in ovulation, experiments were designed to determine the immunohistochemical localization and time specific production of cytokines IL-1 and TNF-$\alpha$ using a mouse model at 36h, 12h, 6h, 2h before ovulation, and at 6h and 18h after ovulation in vivo. Isolated individual follicles in vitro were used to determine more precise roles of cytokines on follicular development, ovulation and steroidogenesis. From these studies it was found that (1) granulosa cells were the primary sites of IL-1$\alpha$ and TNF-$\alpha$ production from large antral follicles and preovulatory follicles in vivo, (2) production of IL-1$\alpha$ and TNF-$\alpha$ increased as ovulation neared, first appearing in the cumulus cells and expanding to antral and mural granulosa cells, (3) less intense staining of these cytokines in the theca layer of smaller follicles suggests that theca cells may contribute to the production of these cytokines to some extent, (4) but there was no IL-1$\beta$ production, (5) localized and temporal production of cytokines during the periovulatory period suggests precise regulation, (6) decrease of IL-1$\alpha$ in the ovary after gonadotropin injection determined by enzyme linked immunoadsorbent assay suggests that IL-1$\alpha$ production may be under the control of gonadotropins, (7) in follicle culture without bone marrow derived cells, granulosa cells were confirmed as the main source of cytokine production, (8) addition of IL-1$\alpha$ and TNF-$\alpha$ to follicles in culture tend to decrease estradiol production. In conclusion, immunoreactive cytokine production correlated positively with the periovulatory follicular development suggesting their role as ovulatory mediators. It requires further studies on what are the signals for the initiation and termination of cytokine production, how transcription and translation of these cytokines are regulated during the periovulatory period, and how they contribute to the ovulation.
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Ackert, Cheryl Lynne. "Postnatal folliculogenesis in the Cx43 null mutant ovary." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/MQ58009.pdf.
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Boisclair, Lachance Jean-François. "Mechanisms of epithelial patterning in the «Drosophila» ovary." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96966.
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Patterning of the Drosophila eggshell requires the induction of dorsal fates in the follicular epithelium of the ovary, which will secrete this eggshell. These fates are induced by the localized activation of epidermal growth factor (Egfr) signaling mediated by its localized ligand Gurken (Grk), which restricts the acquisition of dorsal fates to the dorsal anterior domain of the epithelium. The generation of the complex pattern of fates along the dorsal-ventral (DV) axis has been proposed to be generated by the induction of a second round of Egfr signaling in the follicular epithelium by the late Grk-Egfr signaling. Along the anterior-posterior axis, the restriction of dorsal fates induction to the anterior of the epithelium has been proposed to be mediated by the restriction of Decapentaplegic (Dpp) signaling to the anterior of the tissue. However, some results from the literature cannot be explained by these two models, suggesting that the mechanisms leading to dorsal fates specification are not fully understood. Contrary to these two models, I have shown that a second round of Egfr signaling induced by Grk-Egfr signaling is not required to specify dorsal fates along the DV axis. Instead, my data support the hypothesis that the different levels of Egfr activity generated by the gradient of Grk are sufficient to generate the pattern of fates along the DV axis. Furthermore, my results show that Dpp signaling is not required to restrict dorsal fate acquisition to the anterior of the tissue. Rather, my results suggest that the restriction of competence to induce dorsal fates to the anterior of the epithelium depends on the generation of a posterior refractory fate. My results suggest that it is the absence of the expression of the transcription factor Mirror (Mirr) in response to ectopic Egfr signaling in the posterior domain that restricts dorsal fates acquisition to the anterior domain. Taken together, my results suggest that the competence to express Mirr in the posterior domain is dependent on the early induction of Egfr signaling in this domain. Since only the dorsal-anterior domain is exposed to late Grk-Egfr signaling, Mirr expression is restricted to this domain.La formation des structures dorsales sur la coquille de l'oeuf de la drosophile requiert l'induction de destinées cellulaires dorsales dans l'épithélium folliculaire. L'induction de ces destinées cellulaires dans le domaine dorso-antérieur de l'épithélium folliculaire est médiée par la restriction de l'activation de la voie de signalisation du récepteur du facteur de croissance épidermal (Egfr) par son ligand Gurken (Grk). Un mécanisme a été proposé pour expliquer la génération du patron des destinées cellulaires dorsales sur l'axe dorso-ventral. Ce mécanisme requiert l'induction par la signalisation Grk-Egfr, d'une seconde ronde de signalisation par Egfr dans l'épithélium folliculaire. De plus, un autre modèle propose que la restriction de ces destinées cellulaires est médiée par la restriction de la signalisation Decapentaplegic (Dpp) à l'antérieur de ce tissu. Cependant, certains résultats décrits dans la littérature ne sont pas expliquées par ces deux modèles suggérant que les mécanismes menant à l'induction des destinées cellulaires dorsales ne sont pas bien compris. Mes résultats montrent que la seconde ronde de signalisation Egfr n'est pas requise pour la spécification des destinées cellulaires dorsales. Mes résultats supportent plutôt l'hypothèse que différentes intensités de la signalisation Egfr activée par le gradient de Grk contrôlent l'induction des différentes destinées cellulaires. De plus, mes résultats montrent que la signalisation Dpp n'est pas requise pour la spécification des destinées cellulaires dorsales à l'antérieur du tissu. Mes résultats montrent plutôt que la génération d'une destinée postérieure réfractaire à l'induction des destinées cellulaires dorsales par la signalisation Egfr est responsable de la restriction des destinées dorsales à l'antérieur. Mes résultats suggèrent que la compétence, pour induire les destinées cellulaires dorsales, dépend de l'habileté des cellules pour induire l'expression du facteur de transcription Mirror (Mirr) en réponse à la signalisation Egfr. Dans leur ensemble, mes résultats supportent un modèle où la signalisation Egfr précoce induite par Grk inhibe l'habileté d'induire l'expression de mirr dans le domaine postérieur. Puisque le domaine dorso-antérieur n'est pas exposé au signal précoce, l'induction tardive de la signalisation Egfr par Grk induit l'expression de mirr dans ce domaine.
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Ragoobir, Jennifer. "Lipoproteins and progesterone biosynthesis in the human ovary." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313686.
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Watson, Richard Henry. "Basic fibroblast growth factor in the human ovary." Thesis, University of Southampton, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.297000.
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Goh, Shireen. "Micro-bioreactor design for Chinese hamster ovary cells." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/82368.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2013.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 195-203).
The research objective is to design a micro-bioreactor for the culture of Chinese Hamster Ovary (CHO) cells. There is an increasing demand for upstream development in high-throughput micro-bioreactors specifically for the recombinant CHO cell line, an important cell line for producing recombinant protein therapeutics. In order to translate a micro-bioreactor originally designed by our group for bacteria to CHO cells, there would need to be significant modifications in the design of the micro-bioreactor due to the extreme sensitivity of CHO cells to physical and chemical stresses. Shear stresses inside the growth chamber will have to be reduced by three orders of magnitude. Moreover, the long doubling time of CHO cells requires a 2 weeks long culture. In a high surface to volume ratio micro-bioreactor, evaporation becomes a major problem. Contamination control is also vital for CHO cultures. In addition, the offline sampling volume required for validation necessitates a doubling of the working volume to 2mL. The newly designed Resistive Evaporation Compensated Actuated (RECA) micro-bioreactor is fully characterized in this thesis to ensure that the design meets the physical specifications of the required CHO cell culture conditions. The RECA micro-bioreactor will be tested with industrial recombinant CHO cell lines. This work is done in collaboration with Genzyme, USA and Sanofi-Aventis, Frankfurt. In this thesis, we also propose the use of dielectric spectroscopy electrodes for online cell viability sensing of CHO cells in micro-bioreactors. The electrodes are fabricated on polycarbonate, a biocompatible and optically clear thermoplastic that will be one of the future base material for microfluidic devices which can be rapidly prototyped. To demonstrate the viability of dielectric spectroscopy as an online viability sensor for CHO cells in a micro-bioreactor, the electrodes are used to characterize samples taken daily from a CHO shake flask batch culture without any sample modifications. Two different electrode geometries and correction methods will be compared to find the optimal system for viability measurements in a micro-bioreactor.
by Shireen Goh.
Ph.D.
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Smyth, Christopher David. "Paracrine mechanisms of gonadotrophin action on the ovary." Thesis, University of Edinburgh, 1994. http://hdl.handle.net/1842/20805.
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This thesis describes a study of the role of local regulators in the modulation of gonadotrophin action. It was found that in vivo FSH stimulated granulosa cell proliferation and increased ovarian weight, but was incapable of stimulating granulosa cells to proliferate in vitro. This suggests that the action of FSH in vivo is mediated through another factor. However, in the presence of LH, FSH also stimulated the expression of differentiated functions (progesterone and oestradiol production) both in vivo and in vitro demonstrating a direct effect of FSH. In the absence of LH or aromatase substrate, FSH induced the potential for aromatisation but did not increase uterine weight, a marker of oestradiol production. Therefore it is concluded that FSH is the primary stimulus for follicular development but that LH is also required for co-ordinated follicular development. There is a growing body of indirect evidence to suggest that factors of FSH-stimulated granulosa cell origin may regulate adjacent thecal/interstitial cells. Cytochrome P45017α (17-hydroxylase/C17-20 lyase) in thecal/interstitial cells is a LH-responsive steroidogenic enzyme vital for androgen production. To obtain direct evidence for FSH-stimulated paracrine signalling in the ovary a rat thecal/interstitial cell culture system was validated for the study of the control of androgen production. Using this system and Northern hybridisation the control of androgen production by gonadotrophins and granulosa cell derived factors was studied. The 2.0 kb P45017α mRNA signal in ovarian total RNA from intact animals was dose-dependently increased by treatment with recombinant human FSH (rh-FSH). Treatment of hypophysectomised animals with rh-FSH did not consistently alter ovarian P45017α mRNA levels, though in the presence of low levels of LH, FSH increased P45017α mRNA expression.
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FIORENTINO, GIULIA. "Digital 3D functional atlas of the mouse ovary." Doctoral thesis, Università degli studi di Pavia, 2021. http://hdl.handle.net/11571/1420340.
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L'infertilità femminile è una malattia che colpisce un numero crescente di donne. La chiave per lo sviluppo di strategie per il suo trattamento è aumentare la nostra conoscenza su follicologenesi, maturazione degli oociti e rimodellamento vascolare, in particolare per come si verificano nel loro contesto tridimensionale (3D).
La maggior parte delle informazioni su questi processi è stata ottenuta con approcci che hanno portato alla perdita dell'integrità 3D dell'ovario, alterandone così la naturale organizzazione spaziale degli eventi.
L'obiettivo principale del mio lavoro di tesi è stato costruire un modello 3D in silico dell’ovario di topo e, a tal fine, ho progettato una pipeline organizzata in cinque fasi principali:
1. Fissazione: la prima fase prevede l'isolamento e la fissazione dell'ovario in modo da riutilizzarlo per le analisi ex vivo.
2. Tomografia: La micro-Computed Tomography (microCT) dell'ovario di topo adulto ha consentito l'identificazione, la mappatura 3D e la conta dei follicoli dal secondario al preovulatorio e la ricostruzione del sistema vascolare principale. I risultati hanno mostrato che gli otto settori ovarici, segmentati lungo l'asse dorso-ventrale, ospitano un numero uguale di ciascun tipo di follicolo, suggerendo una distribuzione omogenea del reclutamento e della successiva crescita.
La nanoCT ha consentito la caratterizzazione a singola cellula e la localizzazione dei follicoli appartenenti a tutte le fasi della follicologenesi.
Prese insieme, micro- e nanoCT forniscono la prima ricostruzione isotropica 3D dell'ovario di topo, mantenendo la sua integrità e facilitandone l’analisi con gli altri approcci della pipeline.
3. Tissue Clearing: il metodo iDISCO + combinato con l'imaging confocale 3D dell'intero ovario di topo ha permesso l'identificazione di tutti i tipi di follicoli e del sistema vascolare fino ai capillari più sottili che circondano i singoli follicoli. Grazie all'uso di marcatori molecolari, questo approccio apre la possibilità di rivelare anche informazioni funzionali (ad esempio, la competenza allo sviluppo dei singoli oociti).
4. Spettrometria di massa: L’imaging con spettrometria di massa MALDI (MALDI-MSI) combinato con la cromatografia liquida LC-ESI-MS/MS ha permesso di studiare il proteoma dell'intero ovario di topo e di identificare in situ il profilo peptidico dei tipi follicolari.
La LC-ESI-MS / MS ha generato un elenco di 382 proteine, 75 delle quali svolgono un ruolo chiave nella biologia ovarica. L'analisi delle componenti principali (PCA) confrontando gli spettri di massa MALDI-MSI dei singoli tipi follicolari con quelli dell'intera follicologenesi ha suggerito un cambiamento progressivo nel contenuto di peptidi durante la crescita dal follicolo preantrale al preovulatorio. L’analisi statistica dei follicoli preovulatori T8 ha rivelato 45 proteine differentemente presenti. Di queste, 9 hanno un ruolo specifico nello sviluppo preimpianto (ad esempio, fattori ad effetto materno come DNMT1, NALP5 e KHDC3), suggerendo la presenza di follicoli T8 con diversa competenza allo sviluppo.
5. Istologia: Infine, ho sviluppato un metodo, denominato Confocal Histology, che impiega la proprietà fluorescente dell'Eosina Y insieme ad un'analisi al microscopio confocale di sezioni istologiche di ovario di topo da 20 µm per definire una topografia di tutti i follicoli e per classificare gli oociti contenuti secondo la loro organizzazione cromatinica.
In conclusione, questo lavoro in più fasi serve come proof-of-concept e pone le basi per la costruzione di un Atlante funzionale 3D digitale dell'ovario di topo. Nel prossimo futuro, ho intenzione di utilizzare questa pipeline non solo per migliorare la nostra comprensione delle dinamiche della follicologenesi nell'ovaio in condizioni normali, ma anche durante l'invecchiamento, in presenza di patologie o trattamento ormonale/farmacologico.Female infertility is a disease that affects an increasing number of women. Key to the development of strategies to treat female infertility is to further our understanding of folliculogenesis, oocytes maturation, together with the vasculature remodelling, particularly as they occur in their three-dimensional (3D) environment. Most of our knowledge of these processes has been obtained with approaches that alter the 3D ovary integrity, therefore altering the natural spatial organisation of the events. The main objective of my thesis work was to build an in-silico 3D model of the tiny mouse ovary, and, to this end, I designed a pipeline organised in five main steps: 1. Fixation: The first step involves ovary isolation and fixation so that it can be used for subsequent ex-vivo analyses. 2. Tomography: Computed Tomography (CT) is an X-rays based imaging method which produces a true 3D reconstruction of an object, with cubic voxels and isotropic resolution. At first, MicroCT of the adult mouse ovary allowed the identification, 3D mapping and counting of follicles from the secondary to the preovulatory, and the identification of the major vasculature. Importantly, the eight ovarian sectors, virtually segmented along the dorsal-ventral axis, houses an equal number of each follicle type, suggesting a homogeneous distribution of follicle recruitment and subsequent growth. NanoCT allowed an accurate characterisation and localisation of follicles belonging to all the stages of folliculogenesis. Also, single cells and subcellular components were clearly observable. Taken together, micro- and nanoCT analyses provide the first 3D isotropic reconstruction of the mouse ovary, well maintaining its integrity and facilitating its further analysis with the other approaches described in our pipeline. 3. Tissue Clearing: iDISCO+ combined with the 3D confocal imaging of the whole mouse ovary allowed the identification of all follicle types and of the vasculature down to the thinnest capillaries surrounding individual follicles. Thanks to the use of molecular markers, this approach opens the possibility to reveal functional information (i.e., the developmental competence of individual oocytes). 4. Mass spectrometry: MALDI Mass Spectrometry Imaging (MALDI-MSI) combined with Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS/MS) allowed to investigate the proteome of the entire mouse ovary, and to identify in-situ the peptide signature of follicular types. LC-ESI-MS/MS generated a reference list of 382 proteins, 75 of which playing a key role in ovarian biology. Pricipal component analysis (PCA) comparing the MALDI-MSI mass spectra of individual follicle types with those of the entire folliculogenesis suggested a progressive change in peptide content during follicle growth from the pre-antral follicle to the fully-grown. Interestingly, statistical analysis of T8 follicles, revealed 45 proteins differentially present. Of these, 9 have a specific role in preimplantation development (e.g., maternal effect factors like DNMT1, NALP5 and KHDC3), suggesting the presence of T8 follicles with different developmental competence. 5. Histology: I developed a method, named Confocal Histology, which employs the fluorescent properties of Eosin Y together with a confocal microscopy analysis of 20 µm-thick mouse ovary histological sections, to define a topography of all the ovarian follicles, and to classify the enclosed oocytes according to their chromatin organisation. In conclusion, this multi-step work serves as proof-of-concept and set sound bases for building a digital 3D functional Atlas of the mouse ovary. In the next future, I plan to use this pipeline not only for improving our understanding of folliculogenesis dynamics in the ovary under normal conditions, but also during ageing, in the presence of pathologies or hormones/drugs treatment.
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Caldwell, Aimee Sarah Lee. "Unravelling The Role Of Androgens In Polycystic Ovary Syndrome." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/18129.
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Polycystic Ovary Syndrome (PCOS) is a multifaceted hormonal disorder which affects 5-15% of reproductive-aged women worldwide. While classically recognised as an ovarian disorder, PCOS is associated with a variety of reproductive, endocrine and metabolic features including ovulatory dysfunction, infertility, hyperandrogenism, obesity, and an increased risk of type 2 diabetes mellitus and cardiovascular disease. The most consistently present of these is hyperandrogenism – supraphysiological levels of androgens such as testosterone (T) and dihydrotestosterone (DHT). Typically thought of as male steroid hormones, androgens have been shown to play important role in the maintenance of normal female reproductive function. Despite the high prevalence of hyperandrogenism amongst patients, the role of androgens in the etiology and pathogenesis of PCOS has yet to be determined. The aim of this work was to unravel the association between excess androgen exposure and the development and advancement of the PCOS phenotype in mouse model of androgen-induced PCOS. The first study contained within this work (Chapter Three) provides the first comprehensive characterization of a range of reproductive, endocrine and metabolic traits associated with PCOS in four distinct mouse models: a model of prenatal androgenisation utilising the potent non-aromatizable androgen DHT administered during days 16-18 of gestation, and three diverse models of postnatal androgen exposure employing a long-term treatment with either DHT, the proandrogen dehydroepiandrosterone (DHEA), or letrozole (an aromatase inhibitor) for 90 days beginning at 3 weeks of age. Prenatal androgenisation produced some reproductive and endocrine traits, but failed to induce the metabolic abnormalities seen in PCOS. DHEA treatment did not reproduce any features associated with PCOS while treatment with letrozole produced few PCOS-like characteristics and some aberrant changes not typical of the syndrome. Additionally, letrozole treatment did not reproduce any metabolic attributes of PCOS. On the other hand, postnatal exposure to excess androgen, by way of DHT treatment, produced a breadth of reproductive, endocrine and metabolic traits that mimic those seen in human PCOS. This study revealed that a treatment regime of long-term postnatal exposure to DHT reproduced the strongest PCOS-like phenotype in our mice and provides a robust animal model in which to study the pathogenesis of PCOS. The second study (Chapter Four) aimed to explore the involvement of genomic androgen receptor (AR)-mediated actions in the development of these PCOS traits. As a prenatally androgenised mouse model of PCOS had previously been reported to exhibit impaired neuroendocrine hypothalamic feedback of the hypothalamic-pituitary-gonadal (HPG) axis, we took this opportunity to utilise mice from our own prenatal model to investigate the neuroendocrine regulation of the HPG axis in PCOS in addition to the effects of AR inactivation on the PCOS phenotype. PCOS was induced in wild-type (WT) and androgen receptor knockout (ARKO) mice using DHT administered on days 16-18 of gestation. A subset of these mice were also exposed to 17β-estradiol for 7 days prior to collection, via a subdermal implant, to investigate the impaired estradiol negative feedback on the hypothalamus. WT mice with DHT-induced PCOS displayed several reproductive abnormalities including aberrant cycling and ovulatory dysfunction in addition to adipocyte hypertrophy and hepatic steatosis. However, diestrus serum luteinising hormone and follicle stimulating hormone, and estradiol-induced negative feedback as well as hypothalamic expression of several neuropeptides were unaffected by DHT treatment in WT mice. Mice both homozygous and heterozygous for the global inactivation of the AR (ARKO), did not display any PCOS traits when exposed to excess androgens during prenatal life. This study showed the importance of AR signalling in the development of PCOS and revealed that even AR haplosufficiency is adequate to prevent induction of PCOS by prenatal hyperandrogenism. Finally, the third study (Chapter Five) aimed to shed further light on the AR-mediated androgen actions in PCOS with a focus on identifying the tissue-specific targets of these actions. Employing our postnatal model of PCOS induction, this study investigates the effects of: 1) global loss of AR signalling (ARKO), 2) neuronal knockout (NeurARKO) and 3) granulosa cell-specific AR inactivation (GCARKO) on the development of the PCOS phenotype induced by exposure to exogenous DHT. As in our prenatal model, ARKO mice were fully protected from all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of a variety of reproductive and metabolic traits including classic polycystic ovaries, dysfunctional ovulation, obesity and dyslipidemia. In contrast, loss of AR signalling in granulosa cells did not impede the pathogenesis of PCOS-like features in GCARKO mice. To further examine the role of extra-ovarian AR signalling in PCOS, reciprocal ovary transplants were carried out in WT and ARKO mice. Results from ARKO hosts with transplanted WT ovaries revealed that excess androgen exposure requires functional extra-ovarian, and not intra-ovarian, AR signalling in order to produce features of PCOS. This study provides strong evidence that neuroendocrine genomic AR signaling is an important mediator in the development of PCOS. The studies contained within this thesis are the first to provide a comprehensive analysis of a mouse model of PCOS encompassing a breadth of reproductive, endocrine and metabolic features. This work has identified the optimal model in which to study this complex, multifactorial condition which affects a significant number of women worldwide. Additionally, our results have shown that the effects of androgens on the pathogenesis of PCOS are mediated via the androgen receptor in a dose-dependent manner such that two functional copies are required for DHT to reproduce features of PCOS in the mouse. Finally, in a crucial study to investigate the locus of androgen actions we have revealed the previously overlooked importance of extra-ovarian neuroendocrine androgen action in the origins and progression of PCOS, despite it being thought of primarily as an ovarian disorder. Overall, these studies have provided valuable insights into both the role of androgens in Polycystic Ovary Syndrome and potential new targets for the development of mechanism-based treatments of this disorder.
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Sieben, Nathalie Lucie Gilbert. "Genetic profiling of serous borderline tumors of the ovary /." [S.l. : s.n.], 2005. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=014979802&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Wahlberg, Patrik. "Matrix degrading proteases in the ovary : expression and function." Doctoral thesis, Umeå : Univ, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-280.
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Richard, Martine. "Localization of LHhCG binding sites in the polycystic ovary." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=61954.
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Tullet, Jennifer Marie Anne. "Functional characterisation of the corepressor RIP140 in the ovary." Thesis, Imperial College London, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418096.
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Marsden, Philippa Jane. "Insulin action and ovarian function in polycystic ovary syndrome." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313272.
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Bastock, Rebecca. "Planar polarity signalling in the 'Drosophila' wing and ovary." Thesis, University of Sheffield, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434660.
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Perks, Claire Marie. "The insulin-like growth factors in the ovine ovary." Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259444.
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Hu, S. "Cardiovascular function in pregnant women with polycystic ovary syndrome." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1346456/.
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An association has been proposed between polycystic ovary syndrome (PCOS) and hypertensive disorders of pregnancy, with an increasing body of evidence indicating that PCOS may have significant implications for pregnancy outcomes and long-term health of a woman and her offspring. Whether PCOS itself or the associated conditions, like obesity and fertility treatment, are responsible for these increased risks is a continuing matter of debate. Ambulatory blood pressure and carotid artery elasticity were therefore prospectively investigated in matched PCOS and control pregnancies. Twenty two PCOS–control subject pairs with singleton pregnancies, matched for age, body mass index, parity and ethnicity, were recruited in the first trimester (T1, 11–13 weeks). Ambulatory blood pressure recording for 24 h and carotid artery ultrasound for elasticity estimation and intima media thickness (IMT) were performed in T1 and in the second (T2, 22–24 weeks) and third (T3, 32–34 weeks) trimesters. In addition, endothelial function was examined using post-occlusive reactive hyperaemia (PORH). At nearly all time points during gestation, ambulatory systolic, diastolic and mean arterial pressures were elevated in PCOS versus control pregnancies. Carotid artery stiffness index was greater and compliance was less in PCOS pregnancies compared with controls. Differences in night-time systolic pressure and carotid artery elasticity were greatest in T3. PCOS also increased the incidence of hypertensive disorders of pregnancy. IMT was also higher in PCOS group in all trimesters of pregnancy but there was no significant difference in PORH results in both groups throughout pregnancy. Pregnant women with PCOS have higher baseline ambulatory blood pressure and impaired arterial elasticity, suggestive of disturbed vascular adaptation to pregnancy. The IMT was also higher in pregnant PCOS women, consistent with the notion of increased cardiovascular co-morbities in PCOS.
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Chedumbarum, Pillay O. D. "The association between polycystic ovary syndrome and endometrial cancer." Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/19981/.
Full textAbstract:
HYPOTHESIS: Women suffering from polycystic ovary syndrome have an increased risk of developing endometrial carcinoma. AIM: To determine whether people with polycystic ovary syndrome have an increased risk of developing endometrial carcinoma. BACKGROUND: Endometrial cancer is one of the commonest cancers to occur in women in the Western World and unopposed oestrogen stimulation of the uterus is amongst one of the aetiologies postulated for this condition. It is generally assumed that women with polycystic ovary syndrome are more likely to develop endometrial hyperplasia and carcinoma for the reason mentioned above. The validity of this association has however never been tested. This relationship is investigated within this thesis. METHODS: 1. A case- control study comparing the ovarian morphology of women diagnosed with endometrial carcinoma and those with benign gynaecological conditions. 2. An immunohistochemical study to assess expression of cell cycle and apoptotic proteins (surrogate markers of prognosis) in cases of endometrial carcinoma from women with PCO or from women with normal ovaries. 3. A microarray study of gene expression in the endometrium of cycling and non-cycling women with polycystic ovary syndrome. RESULTS: We found no significant difference in the prevalence of PCO (using this as a marker of PCOS in the absence of information on biochemistry) in the ovaries of patients diagnosed with endometrial cancer compared to women with benign gynaecology disease. Cyclin D1 expression was significantly increased in the endometrial cancers associated with PCO whilst the expression of ki67, Bcl2 and p53 was not significantly different. A total of 101 genes were differentially expressed in the endometrium of women with PCOS with regular cycles, long cycles and simple endometrial hyperplasia. CONCLUSION: Although our numbers were small, these results challenge the assumption that PCOS is a risk factor for endometrial cancer. The raised expression of Cyclin D1 in endometrial cancers associated with PCO suggests that the prognosis for women with PCO is not necessarily better than those without PCO. There were alterations in the expression of genes which affect endometrial function in women with PCOS including those with regular menstrual cycle women. This suggests that the altered hormonal environment has an effect on gene expression at a very early stage which may have an implication on endometrial carcinogenesis.
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Aghilla, Mohamed M. "Inflammation and cardio-metabolic risks in polycystic ovary syndrome." Thesis, University of Warwick, 2012. http://wrap.warwick.ac.uk/50038/.
Full textAbstract:
Polycystic Ovary Syndrome (PCOS) is the most common reproductive and endocrine disorder in females during their reproductive life. The syndrome is characterized by a constellation of symptoms and signs including menstrual disturbance, hyperandrogenism and polycystic ovaries. Other features of PCOS include obesity, metabolic syndrome, insulin resistance and an increased risk of developing diabetes mellitus and cardiovascular disease. Recently, PCOS has been recognized as a low grade inflammatory condition. Several inflammatory markers have been found to be raised in PCOS, such as interleukin-6, tumour necrosis factor-alpha and Interleukin-18. Low grade inflammation may potentially produce an insulin resistant state and promote the development of atherosclerosis. Insulin sensitzers such as metformin and pioglitazone have been shown to have a favourable effect not only on the symptoms of PCOS, but also on the hormonal and metabolic parameters in those subjects. In my thesis I primarily focussed on IL-18, B cells activating factor (BAFF), and the hepatokine, Fetuin-A, all linked to insulin resistance. IL-18 has a strong affinity towards its natural inhibitor, IL-18 binding protein (BP) and binding of IL-18 to IL-18 BP results in neutralization of IL-18, and consequently reduced free IL-18; the active form of the molecule. I have shown that PCOS women have a higher free IL-18, with hyperinsulinaemia the main factor that determines IL-18 in vitro. Furthermore, I have shown that Pioglitazone treatment for 12 weeks decreased both the total and free IL-18 in PCOS women. The reduction of IL-18 was accompanied by an improvement in IR. On the other hand, metformin treatment for six months failed to improve insulin sensitivity and did not influence IL-18 levels. BAFF, a novel adipokine, was studied in PCOS subjects, and I found lower BAFF levels in this cohort of patients. In vivo, BAFF correlated negatively with androgens, and in vitro work revealed that androstenedione as a negative regulatory factor for BAFF production Fetuin-A also known human protein α2-Heremans-Schmid glycoprotein, is a known natural inhibitor for insulin and abundantly expressed and secreted by the liver; fetuin-A has been suggested to act as a link between obesity, insulin resistance and MS. The circulating levels of Fetuin A are increased in women with PCOS, which is more pronounced when associated with MS. Metformin decreases Fetuin A in vivo, and also decreases both the expression and secretion of Fetuin A from HepG2 cells.
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Blair, S. A. "Cardiovascular and Inflammatory Risk Factors in Polycystic Ovary Syndrome." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527660.
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Lakhani, K. "Arterial wall mechanics in women with polycystic ovary syndrome." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1444762/.
Full textAbstract:
Around 20% women of reproductive age are found to have polycystic ovaries (PCO) during ultrasound examinations and approximately 10% have symptoms of polycystic ovary syndrome (PCOS), which is associated with multiple risk factors for cardiovascular disease. The aim of this thesis was to investigate arterial mechanical properties and responsiveness to vasoactive stimuli in young women with PCOS, PCO and controls, using non-invasive ultrasound techniques. The influence of PCOS-related endocrine and metabolic perturbations on aortic function was investigated in a mifepristone-treated rat model of PCOS. The carotid artery pulsatility index was decreased in PCO and PCOS women and there was a paradoxical vasoconstrictor response to a dilator stimulus in these women relative to controls. Vascular compliance was decreased in the internal carotid artery in PCO and PCOS women PCOS women also exhibited increased intima-media thickness (IMT) of the common carotid and common femoral arteries compared with controls. In the cutaneous microcirculation, the response to the vasodilator acetylcholine (ACh) was depressed in PCOS women, whilst the response to sodium nitroprusside (SNP nitric oxide donor - NO) was unaffected. Mifepristone-treated rats exhibited increased serum luteinising hormone, testosterone, and polycystic ovaries. Ultrasound analysis indicated that aortic diameter and blood flow in vivo were unaffected in treated rats, but aortic compliance was reduced. In-vitro assessment of endothelial and vascular smooth muscle function of rat aorta demonstrated decreased relaxation with ACh, which was not abolished by L-NAME, however, the effect of SNP was greater, a finding which raises the possibility of an alternative dilator mechanism that may be independent of NO system. Since increased IMT, endothelial dysfunction and abnormal reactivity are independent risk factors for cardiovascular disease, these results also provide evidence of preclinical atherosclerotic surrogate markers in women with PCOS and PCO. These findings increase the likelihood of an association between PCOS (and probably PCO) and cardiovascular morbidity and mortality.
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Kyriakopoulos, Sarantos. "Amino acid metabolism in Chinese hamster ovary cell culture." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/25143.
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The present thesis focuses on amino acids (a.a.) and their metabolism by Chinese hamster ovary cells, the workhorse of the multibillion dollar biopharmaceutical industry. The aim of the research was to explore a.a. transport and metabolism and define optimal operating conditions during fed-batch culture, which is the most common process mode used industrially. A fast and reliable way to calculate a.a. concentration ranges in media and feeds is of vital importance, as a.a. are the monomers of proteins, which account for 70% of dry cell weight. The desired recombinant product of bioprocesses is typically also a protein. The transport of a.a. into the cells was studied at the mRNA level of a.a. transporters for the first time in a bioprocessing context. The presented results demonstrate that a.a. transport is not the limiting step for recombinant protein formation. Also, the study allowed for a staged feeding strategy to be designed, where a.a. were not fed altogether. Following linear projection of an integral of viable cell concentration target and using the specific a.a. consumption rates during batch culture, six feeds were formulated containing a.a. and glucose. Three designs were based on the results of the a.a. transport study; however, they underperformed in comparison to the other feeds. In the latter, all nutrients were fed at the same time, resulting in cell culture performance comparable to that obtained with a commercial feed that was tested in parallel. This renders the presented method the first to define a traceable quantitative way to calculate amount of nutrients in the feeds. Flux balance analysis, a powerful technique that allows for investigation of intracellular dynamics, was used to analyse the metabolic data. An enhanced intracellular network was created by coupling two pre-existing in the literature that also for the first time included the glycosylation of the host proteins in the biomass equation. Finally, a novel methodology was developed and coded in R to calculate specific rates of consumption/production of various metabolites in cell culture. The methodology couples mass balances for fed-batch culture operation with constructed vectors of the sampling and feeding schemes. This can be further developed to a bioprocess relevant software platform for analysing cell culture data.