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1
Fairs, Nicola Jane. "Steroids and ovarian development in decapod crustacea." Thesis, University of Liverpool, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.277210.
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Uusi-Kerttula, Hanni. "Development of ovarian cancer-targeted adenoviral vectors." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/100129/.
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Ovarian cancer is the deadliest gynaecological cancer, with less than half of patients surviving five years from diagnosis. The asymptomatic nature of the early disease commonly results in diagnosis at an advanced stage where peritoneal metastases are prevalent, and the disease rapidly develops resistance to platinum-based agents. Innovative treatments are needed to combat this untreatable disease that has a poor prognosis. Adenoviruses (Ad) are versatile gene therapy vehicles that have been studied for six decades. Their wider clinical use has been limited by poor tumour-specificity, pre-existing immunity, and toxicity-inducing off-target delivery. We have generated an Ad5.3D.A20 vector that is re-targeted to an epithelial cancer-specific marker, αvβ6 integrin, and fully de-targeted from native interactions ‒ αvβ3/5 integrins, coxsackie and adenovirus receptor (CAR), and human coagulation factor 10 (FX). Ad5.3D.A20 selectively transduced αvβ6+ epithelial ovarian cancer (EOC) cells in vitro and clinical ovarian ascites-derived EOC cells ex vivo, including in the presence of neutralising anti-Ad antibodies. In vivo, Ad5.3D.A20 exhibited significantly reduced off-target accumulation and transduction of the liver, spleen and lungs, relative to Ad5. Efficacy studies are underway to investigate its oncolytic potential. Furthermore, we explored the potential use of alternative serotypes from the rare seroprevalence subgroup D. A novel Ad10 vector showed improved resistance from neutralisation and lack of FX binding. Chimaeric Ad5 vectors pseudotyped with Ad10, -15, -24, -29, -48 or -53 fiber had reduced interactions with CAR, but no binding to CD46. Our strategy for translation initially is via intraperitoneal delivery of oncolytic vectors, bypassingmany of the barriers presented by systemic delivery, but enabling transduction of disseminated metastases. These exquisitely tumour-targeted vectors may be further modulated to carry therapeutic moieties to complement their direct cell-killing activity via the stimulation of anti-cancer immunity. The generated tropism-modified vectors have significant therapeutic potential for a wide range of immuno-oncolytic applications.
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Kanakkaparambil, Raji. "Methyl metabolism and ovarian follicle development in sheep." Thesis, University of Nottingham, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.478930.
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Sefton, Elaine Marie. "Ovarian development in the edible crab, Cancer pagurus." Thesis, University of Liverpool, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426098.
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Wang, Qi. "Chemerin and Prohibitin in the Regulation of Ovarian Follicular Development and their Potential Involvement in Polycystic Ovarian Syndrome." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24098.
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Follicular growth and maturation are tightly regulated processes, which involve the participation of endocrine, autocrineparacrine factors and intracellular molecules. Due to the numerous research efforts, a large number of regulators and their mechanisms of regulation of follicular growth and differentiation have been established. Although the abnormal expression and activities of some of these regulators are believed to be associated with ovarian dysfunction diseases, such as polycystic ovarian syndrome (PCOS), the etiology and pathogenesis of this syndrome are not completely understood.
In this thesis, we have identified two novel regulators of follicular growth and differentiation and examined the cellular and molecular mechanisms that contribute to the folliculogenesis. We present here that chemerin reduces FSH-induced steroidogenic enzyme expression and steroid hormone production in follicles and granulosa cells. Prohibitin expression is upregulated by chemerin and knockdown of prohibitin attenuates the suppressive role of chemerin on steroidogenesis, an action regulated by Akt.
Using an androgenized rodent model, we also present the dysregulation of chemerin and prohibitin and their association with dysregulated follicular steroidogenesis. Our data and preliminary clinical studies demonstrate the potential involvement of chemerin and prohibitin in the etiology of PCOS. These studies significantly improve the knowledge of ovarian functions and the pathophysiology of PCOS, and provide important clues for the development of novel diagnosis biomarkers and new treatment strategies for this complex syndrome.
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Loffler, Kelly Anne. "Molecular genetics of vertebrate sex determination and ovarian development /." St. Lucia, Qld, 2003. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17476.pdf.
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McRae, Thomas Geoffrey, and mikewood@deakin edu au. "Control of ovarian development in the Yabby (Cherax destructor)." Deakin University. School of Ecology and Environment, 1998. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20050825.135944.
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A study under controlled conditions of ovarian development and rematuration in the yabby (Cherax destructot) was undertaken. The purpose of the study was to improve fundamental understanding of the reproductive biology of the species and provide a basis for application to hatchery management in culture.
A review was made of the current status of yabby culture in Australia and the present understanding of reproductive biology of decapod Crustacea. The review emphasised factors controlling several aspects of ovarian development, in particular the processes of vitellogenesis. The subsequent study was designed within the context of current hatchery practice and was based on existing knowledge of decapod reproduction,
The sexual differentiation of the yabby after hatching was investigated by serial histological sections, and experiments were carried out to investigate the possibility of sex reversal of males. Most of this Investigation was concerned with removing the influence of the androgenic gland in directing male development, with the intent of observing the development of the elementary gonadal tissue into ovary. It was found that in contrast to other crustacean species, the sex of the yabby becomes fixed before the development of external secondary sexual characteristics, and before the androgenic gland can be discerned. Ovarian tissue developed in females at less than 8 weeks after hatching. A preliminary examination was undertaken for feminising parasites in gonadal tissue of a hermaphrodite yabby.
Investigation of the ovary after spawning demonstrated that whilst the female was held under constant conditions of temperature and photoperiod, little rematuration occurred. Except for generation of previtellogenic oocytes during the first two days, the gonaciosomatic index remained low for up to 5 months after spawning. If the temperature of the female was reduced to 10°C and maintained constant, the previtellogenic oocytes were partially resorbed over a three week period. Rematuration then commenced, albeit at a low rate because of the reduced temperature,
A method for standardising gonadosomatic indices was developed which took into account differences in hepatopancreatic nutrient reserves of individuals and loss of one
or more appendages. This part of the study also considered constraints to rematuration and developed a method of accounting for differences in the ability of females to remature after spawning.
Experiments were carried out to investigate the effect of crowding and temperature manipulation on initiating ovarian rematuration and to determine the rate of rematuration at 22°C once initiated. The duration of low temperature had no effect on rematuration; an overnight cooling was sufficient to initiate the process, Rematuration to the end of stage 2 vltellogenesis was substantially complete within 10 days. Crowding of females suppressed rematuration, but less than ideal water quality was not found to have any effect. The presence of a male initiated rematuration at a similar rate, but also led to stage 3 vitetlogenesis and spawning. A study was made of the pheromonal influence of the male through water borne factors without success. Rematuration could not be induced in ovigerous females.
The literature review indicated that ovarian rematuration was under the control of an ovary stimulating hormone produced by the thoracic nerve ganglia. Attempts were therefore made to stimulate ovarian rematuration by incorporating the thoracic nerve into the diet of females. Attempts were also made to induce the release of ovary stimulating hormone from the thoracic nerve with 5-hydroxytryptamine, and also with octopamine. No effects were found, but a significant difference between the neurophysiology of the yabby and northern hemisphere crayfish was observed, and the implications of this finding are discussed. The study did not produce any conclusive evidence of an ovary stimulating hormone for the yabby.
A model of ovarian rematuration which collects the findings of the experimental investigations was developed, and was used to suggest a hatchery broodstock management protocol. This model differs from existing models in that rematuration triggers and nutritional status are considered.
8
Leinster, David Amdrew. "Development of an intravital microscopy model of ovarian cancer." Thesis, Queen Mary, University of London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.515152.
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Shuttleworth, Gail. "Porcine ovarian follicle development and the renin-angiotensin system." Thesis, University of Nottingham, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324699.
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Burke, Christopher R. "Regulation of Ovarian Follicular Development with Estradiol in Cattle." The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1054666226.
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Telfer, Evelyn Elizabeth. "Factors influencing follicular development in mammalian ovaries." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/26993.
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The studies described in this thesis have been concerned with several aspects of follicular development in the mammalian ovary. Chapters 2, 3 6 4 deal with mathematical modelling of ovarian follicle dynamics in normal animals and comparisons with experimentally manipulated animals. Chapter 5 describes a novel aethod for estimating the clonal origin of the mouse ovarian follicle. In the final two chapters, the comparative physiology and anatomy of follicular numbers and sizes and the incidence of polyovular follicles are described for a number of species. The unifying theme of these studies is that they reveal patterns existing in follicular development and utllisation by detailed examination of one species, (CBA/ca mouse), and broadly by interspeci,fic comparisons (with relation to scaling). A detailed mathematical description of the follicular dynamics of virgin CBA/ca mice up to 98 days of age has been obtained by the application of compartmental modelling to differential follicle counts. The rates of follicle growth (migration) and death have been estimated for five ?stages of development (primordial to Graafian). The model predicts age changes in follicle growth and death rate, there being transitions in the parameters at 20 days second at 60 days. The parameters for normal animals have been compared with those of anilllals under two experimental conditions: 1) by unilateral ovariectomy at 4-2 days of age, which abruptly halves the numbers of ovarian follicles and alters the ratio of large : small follicles. 2) by blocking ovulation using progesterone implants. The dynamics of follicle growth were altered by both treatments in comparison with the controls. Follicles at all stages of development were affected by unilateral ovariectomy and differences may exist with time. The compensatory response by the remaining ovary was due to a combination of an increased preantral growth rate and a decrease in atresia at antral stages. Earlier stages of follicle development were affected this may have been incidental to the compensatory response. In progesterone treated animals follicles developed through to antral stages when they un~erwent atresia. The effects of treatment were observed at three levels of development: 1) The initiation of growth from the primordial pool, 2) Growth rate of small follicles and 3) deaths at larger stages of follicular development. Longer term observations indicated that these effects may not be constant. The modelling studies have looked at numerical changes in the follicle population with time but a greater understanding of the develomental biology of the follicle is required in order to explain the changes in growth and death rates observed. This problem has been tackled initially by studying the clonal origin of the follicular epithelium. The technique used is based on the principle that cells in females. are generally mosaic as a result of X-chromosome inactivation the use of X linked cell markers phospho-glycerate kinase-1 (PGK-1). Granulosa cells were found to be polyclonal in origin with the number of progenitor cells numbering 5 on average. Analysis of cumulus and mural granulosa cells showed that substantial cell mixing had occurred and cuaulus cells were generally founded by more than one clone. Finally, comparative studies have been conducted to look at scaling of follicle sizes and numbers and of polyovular follicles. Ovarian follicle and oocyte sizes were scaled according to body weight (ranging from .005-500Kg) using data from 22 species. Primordial and Graafian follicle sizes varied with body weight but closer correlations for the latter were obtained when the sum of the surface areas or volUiles for a preovulatory set were considered as opposed to the values for individual follicles. The numbers of nongrowtng follicles 1n reserve at young adult ages were correlated with maximum longevity of the species and related to body weight. The frequency of polyov~lar follicles varied 1n species studied and were most abundant 1n the domestic bitch. The overall incidence of polyovular folUcles 1n young bitches was 14 S, being reduced to 5~ 1n bitches at 7-11 years. The frequency of the various types of polyovular preantral folUcle varied inversely with the numbers of oocytes per follicle.
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Lekola, Khomotso Podile Molvia. "Improvement of cattle oocyte retrieval techniques and hormonal influence on in vitro embryonic development." Thesis, University of Limpopo, 2015. http://hdl.handle.net/10386/1546.
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Thesis (M. Sc. (Animal Production)) -- University of LimpopoThe objectives of this study were: 1) To determine the effect of oocyte retrieval techniques (slicing and aspiration) on the quality and quantity of cattle oocytes, 2) To evaluate the effect of different concentrations of hormones on the maturational rate of cattle oocytes selected by brilliant cresyl blue staining, 3) To evaluate fertilization rate and cleavage/embryonic development of oocytes with or without cumulus cells, and 4) To compare the effect of fresh and frozen thawed semen on the fertilization rate of cattle oocytes. In Experiment 1: oocytes were recovered from abattoir derived ovaries using slicing and aspiration. The recovered oocytes were exposed for 90 minutes to 26μM of brilliant cresyl blue (BCB) stain and classified according to the colour of their cytoplasm: BCB+ (oocytes with blue cytoplasm) and BCB- (unstained oocytes). There was no difference (P>0.05) in the quality of oocytes recovered using slicing (60.7 %) or aspiration (53.7 %) techniques. In experiment 2: The BCB selected and the non-selected immature oocytes were randomly allocated into medium 199 + 10 % fetal bovine serum (FBS) maturation media. The media was supplemented with three different concentrations of hormones as treatments (T). The T1 (0.5 μg/ml of follicle stimulating hormone (FSH), 5mg/ml of luteinizing hormone (LH) and 2 μg/ml of estradiol (E2) as the control group. Then, T2 (1 μg/ml of FSH, 6 mg/ml of LH and 2.5 μg/ml of E2) and T3 (1.5 μg/ml of FSH, 7 mg/ml of LH and 4.5 μg/ml of E2). Maturation rate of oocytes was determined by the protrusion of the first polar bodies 24 hours following in vitro maturation. Treatment 2 yielded higher (P<0.05) maturation rate for both BCB+ (65.6 %) and without BCB (60.3 %) oocytes with T1 giving lower (P<0.05) maturation rate for BCB+ (22 %) and without BCB (16 %) oocytes. However, BCB- oocytes had lower (P<0.05) polar body extrusion (3.03 %, 8.1 % and 2.2 %) for T1, T2 and T3, respectively. In Experiment 3: one group of the presumptive zygotes was denuded of cumulus cells and the other group was cultured with cumulus cells. The presumptive zygotes were in vitro cultured in SOF-BSA and changed to SOF-FBS after 48 hours. High fertilization/cleavage rate was observed in oocytes cultured with cumulus cells (29.0 %) compared to the denuded oocytes (20.0 %) for 2-4 cells stage. Day 7 blastocysts were more (P<0.05) on oocytes cultured with cumulus cells (32 %) compared to denuded oocytes (13 %). In experiment 4: The matured oocytes were fertilized using fresh and frozen thawed semen. The oocytes fertilized with frozen thawed semen obtained a better number of 2-4 cell cleavage (23 %) when compared to fresh semen (19 %). Oocytes that were fertilized with frozen thawed semen also obtained higher morula (13 %) and blastocyst (8 %) compared to fresh semen with morula (3.4 %) and blastocyst (2 %). In conclusion, immature oocytes that were exposed to BCB+ and cultured in M199 supplemented with 10 % FBS, 0.5 μg/ml of FSH, 5 mg/ml of LH and 2 μg/ml of E2 had a higher (P<0.05) number of matured oocytes (extrusion of first polar body) compared to those that were not exposed to BCB (no BCB). Oocytes that were cultured with cumulus cells yielded a higher (P<0.05) number of cleaved embryos compared to the denuded oocytes. Slicing yielded a higher (P<0.05) number of oocytes, however the quality of oocytes recovered was similar compared to those recovered by the aspiration technique (P>0.05). Oocytes fertilized with frozen thawed semen yielded higher (P<0.05) number of 2-4 cell, morula and blastocyst when compared with oocytes that were fertilized using fresh semen. Keywords: ovaries, oocytes, slicing, aspiration, COCs, BCB, polar body and cattle
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Alvaro, Mercadal Béatriz. "Genetic factors involved in the development of premature ovarian insufficiency." Doctoral thesis, Universite Libre de Bruxelles, 2015. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/216836.
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Premature ovarian Insufficiency (POI) is the cessation of the ovarian function before the age of 40, defined by high serum gonadotrophins, low estradiol and amenorrhea for at least 4 months. The etiology may be iatrogenic after a surgery, chemotherapy or radiotherapy treatment, environmental, autoimmune or genetic. However, in most of the cases the cause remains unknown. Clinical and family studies suggest a strong heritability of age at menopause and POI, but the number of genetic causes and genes identified to be involved in human POI remains very small. In POI patients, the two crucial functions of the ovary, hormonal secretion and reproduction, are absent. In the last decades, however, new advances in assisted reproduction techniques have allowed the possibility of carrying pregnancies to POI women, thanks to oocyte donation. The aim of this study was to identify new genetic factors implicated in the development of POI women and to analyse the reproductive possibilities and outcome of women with a genetic cause of POI. For the first part of the study, the DNA of a cohort of POI women recruited in the Fertility Clinic of the Hôpital Erasme of the Université Libre de Bruxelles was used to sequence five candidate genes (FSHR, GDF9, BMP15, AMH and AMHR2) known to be implicated in the ovarian folliculogenesis. The most important findings were two very rare variants and one unknown variant in the AMH gene. The functional study performed with these variants suggested a diminished function of the mutant protein. Furthermore, one of the variants was found in the mother of one of the patients, who was also diagnosed of POI at 32 years old. These arguments strongly suggest that a defective AMH could play a role in the development of POI. This is supported by previous studies with knock out mice models, which show an earlier depletion of the ovarian follicle pool due to a faster recruitment of the primordial follicles that constitute the ovarian reserve. The sequencing of the BMP15 gene led to the identification of two new variants not identified among controls but not predicted to be deleterious. Interestingly, one variant previously reported in POI women and predicted to be deleterious for the protein function, was found in a Sub-Saharan African POI patient as well as in our control cohort. This variant was already studied functionally and shown to have a reduced biological activity. However, we identified this variant in 6% of the Sub-Saharan African control population, which suggests that this is a more prevalent variant in the African genotype and raises up the importance of the ethnicity when studying genetic variants.The sequencing of the other genes (FSHR, GDF9 and AMHR2) did not lead to any association with POI.In the second part of the study, 24 women with Turner syndrome and POI were analysed in terms of reproductive, obstetrical and perinatal outcome after oocyte donation. This specific group of patients was chosen because of their specific systemic anomalies that could interfere with pregnancy outcome and because very few reports have been published on this subject. In the 23 patients finally transferred, the pregnancy rate was similar to that obtained after oocyte donation in other cohorts. There was a miscarriage rate of 23% and a rate of complications of pregnancy as high as 50%, mainly caused by pregnancy-induced hypertensive diseases. Four women at risk of genetic POI were included in the fertility preservation program in order to vitrify their oocytes. Three of them have already vitrified successfully their oocytes but none of them has yet used them.Oocyte vitrification represents a new hope for those women with genetic risk of POI to be able to carry a pregnancy with their own oocytes.In conclusion, three variants of the AMH gene could be implicated in the development of POI as demonstrated by the reduced in vitro bioactivity of the variants and the familial segregation of the cases. Since then, it sounds plausible to propose AMH sequencing in the case of familial POI and secondary amenorrhea.In the BMP15 gene, 2 new variants were predicted to be tolerated. A potentially deleterious variant of the BMP15 gene (L148P) previously associated to POI, was also found in 6% of the Sub-Saharan African controls which suggests that it is a common variant in the African ethnic. No clear association was found between the other tested candidate genes and our POI cohort.Regarding Turner’s Syndrome pregnancies, we can conclude that they are high-risk pregnancies that need of a multidisciplinary follow-up before and during pregnancy.Oocyte cryopreservation represents a new tool to be offered to women at risk of genetic POI to preserve their fertility, but not without previous genetic counselling.Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
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Soboloff, Jonathan. "Regulation of hen granulosa cell fate during ovarian follicular development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0012/NQ38799.pdf.
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Danilovich, Natalia. "Ovarian development and function in follitropin receptor knockout (FORKO) mice." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37647.
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This dissertation examines the ovarian development and function in genetically modified mice that lack FSH receptor (FSH-R) signaling. We propose that a complete or partial loss of FSH-R causes ovarian insufficiency resulting in estrogen deficiency and premature aging in female mice.Targeted disruption of FSH-R caused a gene dose related endocrine and gametogenic abnormality in female mice. The resulting FOllitropin R&barbelow;eceptor K&barbelow;nockO&barbelow;ut (FORKO) mutants were acyclic and infertile due to ovulatory defects, even with very high levels of FSH. Lack of FSH-R signaling in females caused a severe ovarian underdevelopment, producing estrogen deficiency. As a consequence, the null mutants developed obesity and skeletal abnormalities. The expression of nuclear estrogen receptor(s) alpha and beta genes and the corresponding proteins in the ovary and uterus of FORKO mice were maintained intact, as estrogen administration induced uterine growth and decreased accumulation of the adipose tissue. By 12 months of age, 92% of FORKO animals developed ovarian neoplasms of sex cord-stromal type similar to pathology observed in women. Our results showed, for the first time, that the loss of the FSH-R signaling mechanisms predisposes the ovary to molecular and structural changes causing tumor formation.
In contrast to acyclic and infertile FORKO (-/-) females, a phenotype of FORKO mice with a partial (+/-) disruption of the receptor gene exhibits irregular cyclicity and reduced fertility, undergoing early reproductive senescence. Our findings also demonstrate that the loss of a single allele of the FSH receptor gene causes a premature exhaustion of gonadal reserves accompanied by age-related changes in the hypothalamic-pituitary axis.
The study concludes that the FSH receptor signaling offers a protective mechanism, which gradually weakens upon reproductive senescence (menopause in women); therefore this knockout constitutes a unique and promising animal model for studying the physiology and molecular mechanisms of gonadal receptors and hormones.
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Scott, Lucy C. "Biomarker development for gastrointestinal and ovarian cancer : a proteomic approach." Thesis, University of Glasgow, 2010. http://theses.gla.ac.uk/1644/.
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The development of new biomarkers for cancer patients would be advantageous in population screening for the early detection of cancers, pathological diagnosis, assessment of prognosis, tailoring treatment to individuals, and assessment of treatment response. With this in mind different proteomic approaches were used to identify biomarkers which could potentially aid prognosis and predict response in gastrointestinal and ovarian cancer. Raf Kinase Inhibitor Protein (RKIP) was originally purified from bovine brain extracts and named phosphatidylethanolamine-binding protein (PEBP). It has subsequently been shown to be a widely expressed and highly conserved protein. Several recent studies have suggested that RKIP may suppress metastasis in melanoma, prostate, and breast cancer, as reduction or loss of RKIP expression was observed in metastatic cell lines and metastatic tissue. In this part of the project RKIP expression was assessed by immunohistochemistry in tissue microarrays (TMA) from patients with colorectal and ovarian cancer. The results confirmed the findings of earlier studies and suggest that the level of RKIP expression is significantly and inversely associated with metastatic disease and can predict the risk of metastatic relapse in patients with no evidence of metastases at presentation. The level of RKIP expression as a prognostic factor was independent of sex, age, tumour site, mitotic index, lymphovascular invasion and tumour stage. Cytokeratin 18 (CK18) is an epithelial-specific cytokeratin that undergoes cleavage by caspases during apoptosis. Measurement of caspase-cleaved (CK18-NE) or total cytokeratin 18 (CK18) from epithelial-derived tumours could be a simple, non-invasive way to monitor or predict responses to treatment. Soluble plasma CK18-NE and CK18 were measured by ELISA from 73 patients with advanced gastrointestinal adenocarcinomas before treatment and during chemotherapy, as well as 100 healthy volunteers. Both CK18-NE and total CK18 plasma levels were significantly higher in patients compared to the healthy volunteers (p=0.015, p<0.001). The total CK18 baseline plasma levels prior to treatment were significantly higher (p=0.009) in patients who develop progressive disease than those who achieve partial response or stable disease and this correlation was confirmed in an independent validation set. The peak plasma levels of CK18 occurring in any cycle following treatment were also found to be associated with tumour response, but peak levels of CK18-NE did not reach significance (p=0.01, and p=0.07, respectively). A surface-enhanced laser desorption-ionisation mass spectrometry (SELDI-MS) pilot study on serum from 8 oesophageal cancer patients and 8 healthy volunteers revealed a novel biomarker, ~4kDa, downregulated in patients (p=0.012). An expanded 30 tumour/normal study was performed for validation which confirmed the down-regulation of this potential biomarker (p<0.0001). Attempts to identify tentatively suggested that the peptide may be inter-alpha-trypsin inhibitor heavy chain H4 precursor, which was interesting as a cleavage fragment of inter-alpha -trypsin inhibitor heavy chain H4 had been previously found to be up-regulated in patients with ovarian cancer, and down-regulated in patients with breast cancer. However, it was not possible to confidently confirm this identification. In a further part of this study, haptoglobin was found to be significantly more abundant in the serum from patients with oesophageal cancer compared to healthy volunteers. It was straightforward to isolate and identify and would be amenable to immunoassay as there are good antibodies available for confirmation. In conclusion, with the current lack of effective markers of metastatic relapse in colorectal cancer, a straightforward test like RKIP expression in the primary tumour may be a very cost-effective way to identify which patients may derive greater benefit from adjuvant treatment and closer post-operative surveillance, and in patients with advanced gastrointestinal malignancy levels of plasma CK18 are a potential marker of tumour response.
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Muruvi, Wanzirai. "'In vitro' development of early-stage ovarian follicles in sheep." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414245.
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O'Neill, H. C. "Transcriptional regulation of Foxl2 and its role in ovarian development." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1425464/.
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If information is power, then the battle of the sexes has been won for many a year by males, led by SRY and an army of male factors. While many key female-specific genes are known to both promote female development and antagonise these male factors, no one-leader stands out as a sole “switch” governess. Foxl2 is a strong candidate for an ovary-determining and/or anti-testis gene in mammals. Mutations in the gene are associated with premature ovarian failure in women (as part of the Blepharophimosis Ptosis Epicanthus Inversus (BPES) syndrome) and XX male sex reversal in goats with the polled intersex syndrome (PIS). However, despite it being expressed from 12.0 dpc specifically in granulosa cells in the early ovary, no gonadal phenotype is seen in XX mice homozygous for null mutations in Foxl2 until after birth. Wnt signalling is also implicated in repressing testis development, but ovary development still occurs with mutations affecting both Foxl2 and Wnt signalling, suggesting that they are part of a redundant system, with one or more critical additional genes or pathways still to be found. Sox9, together with its close homologues within the SoxE subfamily, Sox8 and 10, are required for Sertoli cell differentiation, typical of the testis, and must be repressed to allow granulosa cell and ovary development. Through examining how these SoxE genes are expressed during development of XX gonads mutant in Foxl2 and/or Wnt signalling, additional complex stage-specific requirements for anti-testis gene activity have been revealed. Two approaches have also been taken to begin to define the regulatory regions driving Foxl2 expression in the ovary, with the long-term aim of unravelling a critical enhancer(s), as a female equivalent of the Sertoli cell-specific Sox9 element TESCO, and identifying the factors that bind to this, which may include missing ovary-determinants. First, a strategy was used that makes no prior assumptions, where BAC sequences flanking Foxl2 were used to drive reporter gene expression in transgenic mice. Preliminary data suggests that a 110 kb BAC can replicate aspects of Foxl2 expression, in ovaries and the pituitary. Secondly, an approach based on genomic studies was employed, which assumes that mutations associated with Foxl2 that lay outside the coding region may directly affect tissue-specific regulatory sequences. The caveat with this approach is that these may be associated with levels of expression, or as chromatin organisers, rather than tissue-specific enhancers. D’haene et al (2009) showed a de novo deletion as small as 7.4 kb, located 283 kb 5’ to FOXL2, was capable of causing BPES in humans, while a 11.7 kb DNA element, reported to affect the transcription of Caprine Foxl2, was deleted in PIS from a region about 200 Kb upstream (Pailhoux et al., 2001). These regions contain many Conserved Non-Coding sequences (CNCs), which, in other loci, have sometimes been implicated in the regulation of gene expression. A 6 kb mouse sequence homologous to the 7.4Kb human region was cloned into EYFP, LacZ and Luciferase reporter vectors, and assayed in cell culture and transgenic mice, where it was shown to be able to drive expression in vivo. The results are discussed with reference to the complex genomic architecture of the Foxl2 locus.
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Swann, Kimberley Marie. "Effects of ovarian stimulation on oocyte development and embryo quality." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/14233/.
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Ovarian stimulation plays a pivotal role in assisted reproductive therapies, to increase the number of embryos available for treatment; however, there is no clear consensus from meta-analyses in the literature which, if any, of the preparations in use are superior in terms of clinical outcomes. The aim of this thesis was to examine the effect of common human gonadotrophin preparations with different half lives and LH activity (hMG, rFSH and Pergoveris) on embryo quality and resulting offspring, compared to non- stimulated negative controls and positive PMSG treated controls, using the mouse model. The studies in this thesis indicated that an LH ceiling threshold is evident during folliculogenesis, where the use of long acting LH preparations resulted in higher numbers of fragmented oocytes, absent of cumulus cells (P<0.001), reduced expression of the pro and anti-angiogenic factors, MYHII and PEDF in cumulus cells (P<0.05), increased embryonic developmental arrest (P<0.001) and perturbed IGF2 (P<0.05) and VEGFA gene expression in resulting blastocysts (P<0.01), compared to negative controls. Use of preparations containing LH bioactivity resulted in offspring with altered total body weight trajectories and internal organ weight abnormalities (P<0.05), which were, in some instances, compounded by in vitro culture. In addition, we elucidated a relationship between FSH half life differences between urinary and recombinant preparations and embryo quality. The urinary human gonadotrophin preparation, hMG, could yield developmentally competent embryos at lower concentrations, than the recombinant Pergoveris treatment. In addition to FSH, these preparations contain LH and both low doses of preparations composed of short half life rFSH and rLH and high doses of preparations containing long acting LH bioactivity, resulted in the highest rates of developmental arrest. These groups were observed to have complete absence of H19 expression. The results of this thesis provide clear evidence that ovarian stimulation does negatively impact the embryo and subsequent offspring and provides support for an LH ceiling threshold, above which detrimental effects occur, both on in vitro embryo development and in vivo foetal development, which later effects postnatal growth.
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Sontakke, Sadanand Dewaji. "Identification and characterisation of microRNAs during bovine ovarian follicular development." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/17963.
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Proper understanding of ovarian follicular and luteal development is essential to improve and optimally control reproductive function in domestic animals and to unravel causes of infertility in animals and humans. MicroRNAs (miRNAs) are key post-transcriptional gene regulators in multiple processes involving tissue growth and differentiation. The studies in this thesis were carried out to identify and characterise expression profiles of miRNAs and their potential roles during ovarian follicular development in the cow. The first study aimed to identify expression profiles of miRNAs during antral follicle growth. Follicles were collected from abattoir ovaries and their status (healthy/atretic) was assessed by measuring steroid levels and aromatase expression. An heterologous microarray approach followed by RT-qPCR validation was used to identify and compare miRNA profiles between large (13–16 mm) healthy and small (4–8 mm) follicles. A unique subset of 7 miRNAs (miR-144, miR-202, miR-210, miR-451, miR-652, miR-873 and miR-876) was identified that were enriched in the Large Healthy follicles relative to small follicles and Large Atretic follicles. Further characterisation revealed that many of these miRNAs were highly expressed in the granulosa compartment of the follicle, predominantly in the mural granulosa cells, indicating their potential involvement in regulating granulosa cell function. Expression patterns of miRNAs in the ovarian tissues were generally reflected in the follicular fluid, thus follicular fluid may be used to monitor follicular health. Finally, tissue-wide screening of miRNAs identified miR-202 as a gonad-specific miRNA in the cow. The aim of the second study was to identify potential roles of the miRNAs enriched in Large Healthy follicles. Using in silico approaches, about 1700 bovine genes were identified as the predicted targets of those miRNAs. Putatively targeted signalling pathways are primarily involved in cell survival, proliferation and differentiation. Further, as expected, top predicted gene targets (SPRED1, ATG7, TGFBR2) showed an expression pattern in follicular tissues that was opposite to the patterns of the targeting miRNAs. However, expression patterns of miR-202 or miR-210 during follicular growth could not be recapitulated in gonadotrophin-stimulated cells in vitro and moreover, over-expression or inhibition of miR-202 in these cells did not result in changes in target mRNA levels. The third study investigated the expression profiles of miRNAs during follicle-luteal transition. Microarray analyses identified 9 miRNAs that were upregulated and 14 miRNAs that were downregulated between Large Healthy follicles and early corpus luteum in the cow. Predicted targets of these miRNAs were associated with signalling pathways involved in cell survival, proliferation and differentiation, indicating that these miRNAs might play significant regulatory roles during ovulation and early luteal development. Further, expression of some of these miRNAs and their putative targets during luteinisation in vivo could be recapitulated in cultured granulosa cells providing a system to study the functional roles of these miRNAs during follicle-luteal development. In summary, this is the first study identifying unique subsets of miRNAs associated with follicular development and the follicle-luteal transition in the cow which may be important for female fertility.
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Ploutarchou, Panayiota. "Effect of oocyte glycoproteins on ovarian follicle development and function." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:ab1bad0c-bb83-48ec-82cc-be122c3dc02e.
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The precise mechanisms that regulate the ovulation rate of species are not entirely understood. The C1galt1 Mutant mouse, in which oocytes lack core 1-derived O-glycans, is characterised by (i) increased fertility, evident from ~40-50% larger litters as a result of increased number of growing follicles and (ii) modified cumulus expansion. Work carried out in this thesis investigated both of these phenotypes and led to the understanding of possible mechanisms involved in increased fertility. Through detailed analysis of the cumulus complex both prior- and post-ovulation in Control mice, novel characteristics regarding the physiology of cumulus expansion have been found. In addition, the analysis of C1galt1 Mutants has revealed that a functional cumulus-oocyte-complex requires the essential components to be present above a minimum threshold level, and thus some variation in ECM composition does not adversely affect oocyte development, ovulation or fertilisation. These data have important implications for IVF and the use of cumulus expansion as a criterion for oocyte assessment. C1galt1 Mutants have (i) altered follicle growth characteristics, (ii) reduction in apoptosis levels and (iii) reduction in AMH levels, all of which could be directly or indirectly contributing to the increased fertility phenotype. These data reveal new and important roles for the oocyte in follicle development and female fertility, providing perspectives for future work in female reproduction.
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Koskela, S. (Sanna). "Granulosa cell anti-Müllerian hormone secretion in ovarian development and disease." Doctoral thesis, Oulun yliopisto, 2013. http://urn.fi/urn:isbn:9789526202853.
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Abstract Anti-Müllerian hormone (AMH) was identified originally in connection with its role in male sexual differentiation. In females, AMH is secreted by ovarian granulosa cells of growing follicles and its serum levels correlate well with the remaining number of follicles, thus reflecting ovarian reserve. The aim of this study was to explore the expression and secretion of AMH in human ovarian development and in various disorders resulting in decreased reproductive function. In fetal ovaries, AMH expression was found to be initiated at midgestation and it increased gradually towards term. In serum samples from infant girls, transient postnatal activation of the pituitary-ovarian axis was found and it occurred later in premature infants, reflected in lower serum AMH levels and lower numbers of growing follicles. This immaturity resulted in insufficient feedback from ovary to pituitary and may explain the higher levels of follicle-stimulating hormone (FSH) in these girls. Ovarian follicle reserve is typically diminished in women with primary ovarian insufficiency (POI). Assay of serum AMH may be used to identify women with POI and existing follicles, as women with FSH receptor mutation who were known to have follicles had serum AMH levels in low normal range and girls/women with Turner syndrome mosaicism had higher serum AMH levels compared with those with other karyotypes. The diagnostics and follow-up of ovarian granulosa cell tumors (GCTs) are challenging as a result of the rarity of the disease and late possible recurrences. Assay of serum AMH combined with assay of the currently used marker inhibin B was shown to improve follow-up of GCTs in individual patients, compared with serum inhibin B measurement alone. The analyses revealed that AMH and inhibin B assays perform similarly in detecting macroscopic tumors. Continuous use of combined hormonal contraceptives inhibited ovarian activity independently of the administration route, as serum AMH levels decreased significantly and similarly during oral, transdermal or vaginal administration. The decrease of serum AMH levels indicates that AMH is secreted partially from FSH-dependent follicles. The study provides novel information on AMH secretion in ovarian development, and the use of AMH assay in assessing ovarian reserve and detecting ovarian disorders such as ovarian insufficiency and GCTsTiivistelmä Naisen munasarjassa munarakkuloiden granuloosasolut erittävät anti-Müllerian hormonia (AMH), ja sen pitoisuudet seerumissa heijastavat jäljellä olevien munarakkuloiden määrää. Tässä tutkimuksessa tarkasteltiin AMH:n eritystä ja ilmentymistä munasarjan kehityksen aikana ja erilaisissa munasarjan toiminnan häiriötiloissa. Tuloksina havaittiin, että AMH:a ilmentyy sikiökaudella munasarjassa jo keskiraskaudesta eteenpäin. Syntymän jälkeen otetuissa seeruminäytteissä todettiin ohimenevä aivolisäkkeen ja munasarjan aktivaatio, joka ilmeni myöhemmin ennenaikaisesti syntyneillä tytöillä. Heillä havaittiin vähemmän kasvavia munarakkuloita ja matalammat seerumin AMH-pitoisuudet syntymän jälkeen kuin täysiaikaisilla tytöillä. Tämä kypsymättömyys johtui todennäköisesti munasarjan riittämättömästä palautejärjestelmästä aivolisäkkeeseen, mikä voi selittää korkeammat follikkelia stimuloivan hormonin (FSH) pitoisuudet ennenaikaisesti syntyneillä tytöillä. Ennenaikainen munasarjojen toiminnan hiipuminen voi johtua esim. kromosomi- tai geenivirheestä. Naisilla, joilla on virheellinen FSH-reseptori, tiedetään olevan munarakkuloita jäljellä, ja tulokset osoittivat seerumin AMH-pitoisuuksien olevan lähes normaali näillä naisilla. Myös tytöillä ja naisilla, joilla on todettu Turnerin oireyhtymän mosaikismi, AMH-pitoisuudet olivat merkittävästi korkeammat verrattuna muihin karyotyyppeihin. Täten AMH-määrityksen avulla voidaan mahdollisesti löytää ennenaikaisesta munasarjojen toiminnan hiipumisesta kärsivien joukosta ne naiset, joilla on vielä jäljellä munarakkuloita. Munasarjan granuloosasolukasvaimen diagnostiikka ja seuranta ovat haastavia kasvaimen myöhäisen uusiutumistaipumuksen ja harvinaisuuden vuoksi. Tulokset osoittivat, että seerumin AMH-määrityksen yhdistäminen tällä hetkellä käytössä olevaan inhibiini B -määritykseen voisi parantaa yksittäisten potilaiden seurantaa makroskooppisen kasvaimen toteamisen osalta. Tutkimus osoitti hormonaalisten yhdistelmäehkäisyvalmisteiden jatkuvan käytön vähentävän munasarjan aktiivisuutta merkittävästi annostelureitistä riippumatta, koska seerumin AMH-pitoisuudet laskivat samalla tavalla ehkäisypilleriä, -rengasta ja -laastaria käyttävillä naisilla. Tutkimus toi uutta tietoa AMH:n erityksestä munasarjan kehityksen aikana sekä AMH-määrityksen käytön mahdollisuuksista munarakkuloiden määrän arvioinnissa ja eri häiriötilojen tunnistamisessa
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Blackwell, Lorna Evelyn. "In vitro growth and development of ovarian follicles for fertility preservation." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/7435/.
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A physiological culture system that supports the in vitro growth (IVG) and development of oocytes would be an invaluable tool for the development and optimisation of fertility preservation techniques. Markers of oocyte, follicle and ovarian stromal tissue normality need to be established to ensure in vitro-derived oocytes are healthy and developmentally competent. A 2-step, physiological IVG system was developed that supported (1) activation, growth and development of ovine primordial follicles in situ over 16-23 days; yielding 37 secondary follicles over 31 repeat cultures and (2) development of in vivo- (n=85) and in vitro-derived secondary follicles to the early antral stage, 25% and 19%, respectively. Step (1) was compared to an accelerated system (n=24), which, unlike the physiological system, resulted in a significant increase (p<0.05) in the proportion of degenerating follicles and decrease (p<0.05) in stromal tissue integrity following 6 days culture compared to day 0 control tissue. In addition a significantly higher yield of transitional (p<0.01) and secondary (p<0.05) follicles resulted from the physiological vs. the accelerated system. The expression patterns of 20 genes key to oogenesis and folliculogenesis were established in vivo and compared to stage-matched samples derived using the physiological IVG system, revealing significant changes (p<0.05) in the expression of AMH, IGF1, INHα, INHβA, FST, ZP2, GTSF1, BMP6, BMP15 and MEST. Step (1) was used to evaluate damage to oocyte and ovarian tissue health following the perfusion of 48 ovaries, with either 1.5M dimethyl sulphoxide (DMSO) or L-15 control medium, in combination with the use of NMR spectroscopy to determine the level of DMSO permeation. Perfusion times of 10 and 60 minutes were required permeate the pedicle and cortex tissue, respectively, however, 60 minutes perfusion resulted in a significant decrease in follicle number (p<0.01) and stromal tissue integrity (p<0.05). The overall results indicate that the IVG of oocytes is a suitable tool to both assess the patency of fertility preservation systems and as a means to restore female fertility.
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Karakji, Eli Gabriel. "Regulation of the rat ovarian plasminogen activator system during follicular development." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/10314.
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Successful ovarian follicular growth and ovulation require controlled and directional proteolytic activity for cell migration and follicular wall rapture. Plasminogen activator (PA) system is known to be involved in tissue remodelling during various physiologic and pathologic processes. PA system comprises two activators (tissue-type, tPA and urokinase-type, uPA), three inhibitors (PAI-1, PAI-2 and protein nexin-I) and one receptor (uPAR). In vivo expression of the PA system during follicular development was studied in the immature female rat. Whereas tPA, PAI and uPAR mRNA expression and protein distribution increased in both granulosa and theca-interstitial layers during follicular maturation and reached maximum levels during the preovulatory period, the opposite was true for uPA. Urokinase PA was highly expressed at early stage of development and markedly decreased prior to the expected time of ovulation. Net secreted PA (PAs) and cell associated PA (PAc) activities were higher in differentiated cells and PAs accounted for 70-80% of the total PA activity in both cell stages of follicular development. Our results suggest that (1) a coordinated expression of ovarian PA system exists during follicular development when granulosa cells undergo transformation from undifferentiated and proliferatively active cells to highly differentiated but mitogenically relatively quiescent ones, and (2) in addition to gonadotropins, several intra-ovarian factors play an important role in the regulation of the ovarian PA system during follicular development. (Abstract shortened by UMI.)
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Jefferson, Wendy Noble. "Neonatal Exposure to the Phytoestrogen Genistein Alters Ovarian Differentiation and Development." NCSU, 2005. http://www.lib.ncsu.edu/theses/available/etd-09262005-095720/.
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Genistein, the primary phytoestrogen in soy, was investigated for potential adverse effects on the developing female reproductive system with particular focus on the ovary. Mice were treated with genistein at doses that span the range of human exposure including vegetarian mothers during pregnancy and lactation to infants on soy based infant formulas. Neonatal genistein exposure caused the formation of multi-oocyte follicles (MOFs) in the ovary. This effect is mediated by ERâ as mice lacking this receptor do not develop MOFs while mice lacking ERá do. Further study of genistein?s effects on the ovary revealed inhibition of neonatal oocyte nest breakdown; oocytes were still attached by intercellular bridges and the normal progression of apoptosis was attenuated. Mechanistic studies of MOF formation revealed alterations in cell adhesion molecules. In addition, genistein is not unique in its ability to cause ovarian disruption; other environmental estrogens caused MOFs as well as altered cell adhesion molecule expression. Further, these effects appear to be exacerbated by preferential binding to ERâ. Assessment of reproductive function showed that mice treated with genistein (0.5 and 5 mg/kg) showed signs of early reproductive senescence while mice treated with genistein (50 mg/kg) exhibited infertility characterized by fewer, smaller, implantation sites as well as reabsorptions; ovaries from these mice had no corpora lutea. Stimulation with exogenous gonadotropins restored ovulation, suggesting problems with the hypothalamic-gonadal axis. These data taken together demonstrate that neonatal exposure to genistein at environmentally relevant doses causes adverse effects on the developing reproductive system and in particular on the ovary.
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Cotterill, Matthew. "Gene function during the development of ovine oocytes and ovarian follicles." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496543.
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Wainright, Geoffrey. "Hormonal control of ovarian development in the edible crab, Cancer pagurus." Thesis, University of Liverpool, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283064.
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Chudasama, Dimple. "Discovery and development of liquid biomarkers for ovarian and lung cancer." Thesis, Brunel University, 2018. http://bura.brunel.ac.uk/handle/2438/16174.
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Survival rates in cancers have improved vastly over the years. However, some survival rates remain extremely low, as is the case for ovarian and lung cancer. The lack of robust and reliable biomarkers is strongly reflected in the absence of pre-screening programs, and as such, most patients in these cancer types are diagnosed only in advanced stages, leaving few treatment options. Moreover, relapse and resistance to therapies adds to the complexities of treating these diseases, even in the era of targeted drug development. Research has shown the presence of cancer material, in the form of circulating cancer cells (CTCs) and genomic material in the blood of patients, opening the possibility of 'liquid biopsies'. Liquid biopsies allow sampling of the disease to provide phenotypic and genomic data on the cancer in real-time and on a routine basis. Moreover, they overcome obstacles currently faced by conventional tissue biopsies. In this work we evaluate the use of a novel CTC imaging flow-cytometry platform, and report the ability to characterise and quantify these cells in blood samples. Moreover, we report significantly higher levels of CTCs in cancer patients compared to controls, and found them to be associated with a poorer prognosis. In particular, in lung cancer we observe these findings even in the early stages, suggesting a potential diagnostic use for this assay. We detect a similar trend in when analysing the ctDNA and suggest the possibility of using this technique with a prognostic value in the advanced setting. We also report on the analysis of existing microarray data by use of unique gene regulatory networks to identify biomarkers of interest. RAD51AP1 was identified by this process. Clinical validation revealed an over-expression of this gene in both tissue and blood of ovarian and lung cancers. Moreover, the gene over-expression was associated with a poor overall survival. Functional analysis in vitro revealed silencing RAD51AP1 suppressed tumour growth, in addition, various tumorigenic proteins were down-regulated, whilst apoptotic and immune genes were up-regulated. These results suggest a role for RAD51AP1 as a potential therapeutic target. In this study, we also demonstrate the ability to further exploit tumour genomic material in the blood by means of RNAseq, cancer panels, and CNI scoring to identify novel markers, that play an important role in disease genesis and evolution. RNAseq analysis identified XIST as a gene up-regulated in the blood and tissue of lung cancers. The ovarian cancer panels revealed 2 unique gene signatures in the ovarian cancer patients. With the CNI analyses also highlighting chromosomal aberrations from plasma analysis of cancer patients. Collectively, the use of all these techniques and exploitation of available blood based biomarkers could see significant improvements to survival rates in these, currently devastating diseases.
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McLaughlin, Marie. "Factors affecting in vitro development of bovine and human ovarian follicles." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/15350.
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Meerasahib, Mohamed Fareez. "Development and applications of monoclonal antibodies to TGFβ superfamily members involved in ovarian follicular development." Thesis, Oxford Brookes University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432722.
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Hayes, Eleanor. "Reproductive physiology and age determination in females of the bowfly, Lucilia sericata (Meigen) (Diptera: Calliphoridae)." Thesis, University of Bristol, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265385.
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Smits, Stephanie. "Development of an ovarian cancer symptom awareness tool with tailored content for women at increased genetic risk of developing ovarian cancer." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/68779/.
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In the absence of a routine ovarian screening programme, ovarian cancer symptom awareness is a potential route to earlier symptomatic presentation and disease diagnosis. However, materials to support this strategy may need to be tailored according to risk. The work presented in this thesis identified the contributors to anticipated symptomatic presentation for women at increased genetic risk of ovarian cancer. A mixed-method approach was used to identify determinants of anticipated symptomatic presentation, and included a systematic search of existing ovarian cancer symptom awareness tools, cross-sectional surveys with two risk populations and qualitative interviews with women at increased genetic risk. Additionally, a systematic search and a virtual reference group were used to identify symptom content. Cognitive interviews were undertaken to pilot the draft tool for acceptability and usability with a sample of potential users and providers. Endorsing more benefits than barriers to presentation was associated with earlier anticipated presentation in both risk populations; however, differential effects of underlying health beliefs on anticipated presentation were also identified. In those at increased genetic risk, emotional (worry) rather than cognitive aspects of risk perception predominate in influencing earlier anticipated presentation. Interviews with women at increased genetic risk revealed that personal experience with ovarian cancer shaped beliefs about the disease. The identified health beliefs were incorporated into OvSTAT (ovarian cancer symptom awareness tool), with core content applicable for women from the general population and tailored content to address the specific needs of women at increased genetic risk. OvSTAT was well received in user testing. Overall, the findings suggest that the emotional representation of risk distinguishes earlier anticipated presentation in women at increased genetic risk from that in the general population. OvSTAT could be a mechanism through which appropriate symptomatic presentation is improved, by helping women to manage worry associated with their increased genetic risk status.
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Young, Anna-Mary. "Development of an immunocompetent model of oncolytic adenoviral gene therapy for ovarian cancer." Thesis, Queen Mary, University of London, 2012. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8365.
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Oncolytic adenoviral gene therapy has potential as a novel anti-cancer agent for ovarian cancer. Host immune responses are thought to contribute to its therapeutic effects. However further evaluation has been hampered by the lack of an immunocompetent animal model. This is predominantly because human adenovirus is highly species-specific and replicates poorly in murine cells. The second generation human adenovirus (hAd5) type 5 mutant dl922-947 contains a deletion in the E1A CR2 region which allows it to replicate selectively in cells with Rb pathway abnormalities, a finding observed in >90% of human cancers. Previous work has shown that dl922-947 has considerable activity in ovarian cancer and is more potent than E1A wild-type adenoviruses and the E1B-55K mutant dl1520 (Onyx-015, H101). Unfortunately, like its wild-type counterpart, dl922-947 replicates poorly in murine cells and infectious virion progeny are not generated. Mechanisms for the failure of infectious virion formation remain unclear and have been investigated as part of this project. I have found that murine malignant cells can be infected readily with hAd5 vectors. Both early and late viral genes are transcribed and there is evidence of viral genome replication. However, a profound failure of infective virion production is observed together with low levels of late viral protein expression. Ribosome fractionation assays show reduced viral mRNA loading in murine cells, resulting in failure of translation, especially of late transcripts. Aberrant function of the non-structural L4 protein 100K has been identified as a major hurdle to successful viral replication in murine cells. Ectopic expression of L4 100K promotes translation of viral late mRNA and increases expression of late viral proteins and virion production. However, these increases are only partial.
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Yun, Young Won. "The effects of superovulation on ovarian function and embryo development in rats." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/29326.
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This study examined primary defects and related mechanisms leading to impaired fertility following superovulation with exogenous gonadotropin. Experiments were designed to address the ovulatory response, oocyte quality (gross morphology and nuclear maturation) and embryo development with reference to ovarian steroid and circulating LH levels in immature rats treated with 4, 20 or 40 IU pregnant mare's serum gonadotropin (PMSG).
Superovulatory doses (20 and 40 IU) of PMSG induced the first ovulation as early as 24 hr and prolonged multiple ovulations with two increases: one before 36 hr and the other after 48 hr, while a low dose (4 IU) of PMSG induced a burst of ovulation between 60 and 72 hr. The biphasic superovulatory response was paralleled with two distinct luteinizing hormone (LH) peaks in circulating blood. Early ovulation could be, in part, due to the exogenous LH activity derived from high doses of PMSG. The initial prolonged elevation of serum LH before 54 hr resulted from actual cross-reaction of the injected PMSG with LH antibody in the assay and was dose-dependent, while a precipitous second elevation between 54 and 60 hr resulted primarily from an endogenous LH surge. Additionally, the observation of a marked ovulation inhibition by using a progesterone antagonist (RU 486) and an estrogen antagonist (tamoxifen) indicated the active participation of progesterone as well as estrogen in the PMSG-induced ovulation.
A dose-dependent increase in the percentage of degenerate oocytes following superovulation was noticed from 36 hr onwards and positively correlated with the timing of increased levels of ovarian and serum androgens. Furthermore, superovulated oocytes with even normal appearance displayed substantially different stages of nuclear maturation varying from prophase I to metaphase II, while a majority of control oocytes (4 IU PMSG) was synchronized at metaphase II. The incidence of meiotically aberrant oocytes in superovulated rats was closely associated with abnormal follicular steroidogenesis, i.e. a marked alteration of follicular contents of progesterone and particularly androgens and/or a consistent disruption of sequential changes in overall ratios of androgens/17β-estradiol, progesterone/17β-estradiol and progesterone/androgens.
Administration of an androgen antagonist (flutamide) in superovulated rats significantly reduced the proportion of degenerate oocytes and cellular degeneration of preimplantation embryos, and improved the developmental potential (embryo cleavage), at least in part, via decreased production of ovarian androgens. These results reflect a significant role of augmented ovarian androgen secretion in the perturbation of oocyte quality and subsequent embryo development following superovulation. However, the pharmacological effects of flutamide were restricted to early stage (Day 2) of pregnancy. Therefore, the actual improvement of the quality or development of early embryos by flutamide was ascribed to a substantial reduction of abnormal oocytes before fertilization.
The results of an experiment using the RU486 and tamoxifen indicated that estrogen, but not progesterone, influenced oocyte quality in superovulated rats. RU486 treatment did not affect the oocyte morphology, but tamoxifen treatment was associated with a marked increase in the percentage of degenerate oocytes. The results of this research provide direct evidence of atypical ovulations of superovulated oocytes with premature or asynchronous nuclear maturation as a primary defect leading to impaired fertility including abnormal embryo development, and demonstrate a close relationship between meiotically aberrant oocytes and abnormal follicular steroidogenesis in superovulated rats. Increased levels of ovarian and circulating androgens preceding fertilization were particularly implicated in the perturbation of oocyte quality and embryo development following superovulation. Finally, the process of multiple ovulations induced by superovulatory doses of PMSG appears to involve the exogenous LH activity of PMSG as well as active participation of progesterone and estrogen.Medicine, Faculty of
Obstetrics and Gynaecology, Department of
Graduate
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Enshaei, Amir. "Development of Artificial Intelligence systems as a prediction tool in ovarian cancer." Thesis, University of Newcastle Upon Tyne, 2012. http://hdl.handle.net/10443/1552.
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Ovarian cancer is the 5th most common cancer in females and the UK has one of the highest incident rates in Europe. In the UK only 36% of patients will live for at least 5 years after diagnosis. The number of prognostic markers, treatments and the sequences of treatments in ovarian cancer are rising. Therefore, it is getting more difficult for the human brain to perform clinical decision making. There is a need for an expert computer system (e.g. Artificial Intelligence (AI)), which is capable of investigating the possible outcomes for each marker, treatment and sequence of treatment. Such expert systems may provide a tool which could help clinicians to analyse and predict outcome using different treatment pathways. Whilst prediction of overall survival of a patient is difficult there may be some benefits, as this not only is useful information for the patient but may also determine treatment modality. In this project a dataset was constructed of 352 patients who had been treated at a single centre. Clinical data were extracted from the health records. Expert systems were then investigated to determine the optimum model to predict overall survival of a patient. The five year survival period (a standard survival outcome measure in cancer research) was investigated; in addition, the system was developed with the flexibility to predict patient survival rates for many other categories. Comparisons with currently used prognostic models in ovarian cancer demonstrated a significant improvement in performance for the AI model (Area under the Curve (AUC) of 0.72 for AI and AUC of 0.62 for the statistical model). Using various methods, the most important variables in this prediction were identified as: FIGO stage, outcome of the surgery and CA125. This research investigated the effects of increasing the number of cases in prediction models. Results indicated that by increasing the number of cases, the prediction performance improved. Categorization of continuous data did not improve the prediction performance. The project next investigated the possibility of predicting surgical outcomes in ovarian cancer using AI, based on the variables that are available for clinicians prior to the surgery. Such a tool could have direct clinical relevance. Diverse models that can predict the outcome of the surgery were investigated and developed. The developed AI models were also compared against the standard statistical prediction model, which demonstrated that the AI model outperformed the statistical prediction model: the prediction of all outcomes (complete or optimal or suboptimal) (AUC of AI: 0.71 and AUC of statistical model: 0.51), the prediction of complete or optimal cytoreduction versus suboptimal cytoreduction (AUC of AI: 0.73 and AUC of statistical model: 0.50) and finally the prediction of complete cytoreduction versus optimal or suboptimal cytoreduction (AUC of AI: 0.79 and AUC of statistical model: 0.47). The most important variables for this prediction were identified as: FIGO stage, tumour grade and histology. The application of transcriptomic analysis to cancer research raises the question of which genes are significantly involved in a particular cancer and which genes can accurately predict survival outcomes in a given cancer. Therefore, AI techniques were employed to identify the most important genes for the prediction of Homologous Recombination (HR), an important DNA repair pathway in ovarian cancer, identifying LIG1 and POLD3 as novel prognostic biomarkers. Finally, AI models were used to predict the HR status for any given patient (AUC: 0.87). This project has demonstrated that AI may have an important role in ovarian cancer. AI systems may provide tools to help clinicians and research in ovarian cancer and may allow more informed decisions resulting in better management of this cancer.
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Kuiper, Marcel. "Pre-clinical studies for development of immune gene therapy of ovarian cancer." Thesis, King's College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.299064.
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Stilgenbauer, Morgan Grasselli. "Development of New Platinum-Based Anticancer Agents Targeting Ovarian Cancer Stem Cells." Kent State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=kent1595328319619319.
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Ferraz, Danilo Ribeiro 1986. "Atratividade de iscas de origem animal para dípteros muscóides em área de cerrado do sudeste brasileiro, com ênfase na família Calliphoridae." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314359.
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Orientador: Arício Xavier LinharesDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Os insetos apresentam importância do ponto de vista forense, possibilitando coletar evidências e informações essenciais à justiça. Para o aprimoramento das aplicações da entomologia forense é de extrema importância que sejam realizados estudos relacionados a fisiologia, taxonomia, ecologia, comportamento e distribuição da entomofauna decompositora. Dentre os insetos necrófagos, califorídeos (Diptera) apresentam grande destaque, pois produtos de origem animal são substratos para oviposição e fonte de proteínas e carboidratos para adultos, além de constituir recurso alimentar para larvas de algumas espécies. Os califorídeos passam por diferentes fases de desenvolvimento ovariano sendo que, nos estágios intermediários de desenvolvimento, há intensa deposição de vitelo pelas células tróficas. Assim, com fim de contribuir para um maior entendimento fisiológico e comportamental da família, o presente estudo objetiva avaliar e comparar sua riqueza, observando o padrão de atratividade exercido sobre moscas varejeiras por três diferentes substratos de origem animal (frango, peixe e roedor), bem como os estágios de desenvolvimento ovariano no qual os espécimes coletados se encontravam. Ao todo foram coletados 12.332 espécimes, dos quais 1.432 pertenciam a Calliphoridae. As iscas de moela de frango foram mais atrativas a ordem Diptera, ao passo que a família Calliphoridae foi mais atraída por iscas de roedor. Neste trabalho, 803 fêmeas foram dissecadas, sendo que grande parte destas fêmeas encontravam-se em estágio de vitelogênese completa demostrando a importância da proteína animal como substratos para oviposição
Abstract: Insects are of great forensic importance because they can serve as evidence and provide essential information to justice. In order to improve the applications of forensic entomology, it is of great important to study the biology, ecology, physiology, taxonomy, behavior and distribution of insect fauna associated to decomposing animal matter. Among the scavenger insects, the calliphorids (Diptera) are very important, because many species utilize animal tissues as source of protein and for immature development. Baits of animal origin can act as substrat for oviposition and as source of proteins and carbohydrates for the adults and for larval development feeding .Ovaries of calliphorids undergo different ovarian development phases from the pre-viteloogenic stage to mature eggs. Intermediate phases are characterized by deposition of yolk by the nurse cells. Thus, this study, aimed to contribute to the understanding of the physiological and behavioral characteristics of species of calliphorids, presenting and comparing species richness, attractiveness patterns of three different baits of animal origin these flies (chicken gizzard, fish and rat) as well as the stages of ovarian development in which the collected specimens were found. In all, 12,332 specimens were collected, of which 1,432 belonged to Calliphoridae. The rodent bait was the most attractive to this family while chicken gizzard was more attractive to Diptera as a whole. In this work, 803 females were dissected. The majority of these were in the stage of mature egg, indicating the use of the substracts for oviposition, although this pattern changed depending on the species analyzed
Mestrado
Biodiversidade Animal
Mestre em Biologia Animal
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Rajareddy, Singareddy. "Studies of phosphatidylinositol 3 kinase (PI3K) signaling pathway in mammalian ovarian follicle activation and development." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1378.
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Mukhopadhyay, Asima. "Development of a functional assay to test for homologous recombination in ovarian cancer." Thesis, University of Newcastle Upon Tyne, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.577481.
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Background: PARP inhibitors selectively target homologous recombination (HR) defective cells and show good clinical activity in hereditary breast and ovarian cancer associated with BRCAl12 mutations. A high proportion (up to 50%) of sporadic epithelial ovarian cancers (EOC) could be deficient in HR due to genetic or epigenetic inactivation of BR CA 112 or other HR genes. Therefore there is a potential for extending the use of P ARP inhibitors to these patients if HR status can be identified. Aims: To develop a functional assay of HR status that correlates with sensitivity to the PARP inhibitor AG014699. Methods: Primary cultures were derived from ascitic fluid from patients with EOCs. HR status was investigated by yH2AX and RAD51 focus formation by immunofluorescence. Cytotoxicity to the PARP inhibitor AG014699 was tested by SRB and cell survival assay. Clinical outcome and platinum sensitivity was correlated prospectively with predicted HR status. Results: The success rate of generating primary cultures (n=75) was> 90%. 48 EOCs were evaluated for HR status and cytotoxicity; HR deficiency (HRD) was predicted in 25/48(52%) cultures showing no increase in RAD51 foci. Cytotoxicity was observed in 23/25 HR deficient (PPV-93%) but none of 23 HR competent (NPV-I00%) cultures. 35 patients completed clinical follow up; compared to HR competent patients (n=18), the HR deficient group (n=17) were predominantly serous (p=0.041), sensitive to platinum (58.8% vs. 29.4%) with lower tumour progression rates at 6 months (5.9% vs. 27.8%) and lower death rates at 12 months (17.6% vs. 44.4%). Conclusion: HR status can be determined in primary cancer samples by RAD51 focus formation. 50% EOCs appear to have HR defects. HRD as predicted by the RAD51 assay correlates with ex vivo PARP inhibitor sensitivity, clinical platinum sensitivity and improved survival outcome.
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Salmon, Nicholas Alan. "Oocyte regulation of granulosa cell gene expression during ovarian follicle development in mice." Thesis, University of Leeds, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410899.
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Jenkins, Julian Michael. "The development and influence of functional ovarian cysts during in vitro fertilisation cycles." Thesis, University of Southampton, 1992. https://eprints.soton.ac.uk/421964/.
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Schauer, Stephanie Nicole. "Role of luteinising hormone in ovarian follicle development and maturation in the mare." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/11731.
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Luteinising hormone (LH) is a crucial regulator of ovarian follicle maturation, ovulation and luteinisation. Development of healthy follicles and fertile ovulation can only occur within a specific range of circulating LH concentrations, with differing upper and lower limits depending on the stage of the oestrous cycle. The objective of the three studies in this thesis was to investigate the effects of both physiological and non-physiological circulating LH levels on equine follicular maturity by examining ovulatory and steroidogenic capacity, gene expression profiles and miRNA expression in ovulatory-size follicles at various stages of the oestrous cycle and/or in response to supplementation with LH. The aim of the first study was to investigate the hypothesis that deficient circulating LH is a primary cause for the inability of equine follicles to ovulate during the physiological anovulatory season. A LH-rich equine pituitary fraction (eLH) given twice daily to early transitional mares did not restore steroidogenic capacity of the ovulatory-size follicle or advance the onset of the natural breeding season; however, it significantly stimulated follicular growth to a level similar to that occurring during the normal oestrous cycle. The results demonstrated that a deficiency in LH is critically involved in reduced follicle growth during the anovulatory season. The second study examined the effects of elevated circulating LH levels early during follicle development on follicle maturation and ovulatory ability in cycling mares, with the hypothesis that excessive LH would disrupt ovulation and produce haemorrhagic anovulatory follicles (HAFs). Treatment with eLH or a luteolytic dose of prostaglandin F2α (to stimulate an increase in endogenous levels of LH) did not have any effects on follicle growth or ovulation, but did impair follicular production of androstenedione and insulin-like growth factor 1 (IGF1), suggesting a deleterious effect of high LH on follicle and oocyte maturation. The third study examined the expression of different follicular factors associated with follicle maturation as well as microRNAs (miRNAs) in ovulatory-size follicles naturally developing under different LH milieus (oestrus, dioestrus and spring transitional period). Progesterone and IGF1 were significantly reduced in follicles developing in a low LH environment (dioestrus and transition). All four miRNAs measured, miR-378, miR-542, miR-202 and miR-21 were found at higher levels in subordinate follicles than in preovulatory follicles during oestrus. In addition miR- 202 and miR-21 were significantly increased in transitional follicles relative to oestrous follicles. The results of this study indicate that follicles developing during both the spring transitional and dioestrous periods are developmentally immature and suggested potential important roles of miRNAs in follicle maturation in the horse. In summary, although LH is a key factor promoting follicular growth, it is by itself not sufficient to restore steroidogenic activity in transitional follicles. Elevated LH levels during follicle development do not disrupt ovulation, but induce changes in follicular fluid factors related to follicle maturation and oocyte quality. Follicles developing under different LH milieus show altered miRNA expression, suggesting an important role of miRNAs in follicle maturation.
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Burroughs, Kevin Dale. "The role of ovarian hormones in the development and growth of uterine leiomyoma /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Elvington, Elizabeth Ashcraft Savage. "Contactless Dielectrophoresis towards Drug Screening and Microdevice Development for Cell Sorting." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/23294.
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Firstly, this work demonstrates that contactless dielectrophoresis (cDEP) was useful to detect a reversal in the electrical phenotype of late-stage ovarian cancer cells to a profile similar to that of slow-growing early-stage ovarian epithelial cells after treatment with a non-toxic bioactive metabolite, sphingosine. Current chemotherapeutics are highly toxic to patients and can cause severe adverse side effects, so non-toxic treatments that could slow or reverse cancer growth would be advantageous. This is the first instance of cDEP for detecting induced changes in cell structure, showing its potential as a rapid, non-biomarker-based drug screening platform. Specifically, low frequency contactless dielectrophoresis devices previously designed by Sano et al were used to extract the crossover frequency and specific membrane capacitance of early and late stage mouse ovarian surface epithelial (MOSE-E and MOSE-L) cells when untreated, treated with the anti-cancer sphingosine (So) metabolite and with a generally cancer-supporting sphingosine-1-phosphate (S1P) metabolite. The specific membrane capacitance of MOSE-L cells treated with So decreased and the normalized crossover frequency increased to levels matching MOSE-E cells.
Secondly, a new multilayer cDEP device featuring curved interdigitated electrode channels overlaying a straight sample channel for the purpose of cell sorting was designed, computationally modeled, fabricated, and tested. The goal of this design was to achieve continuous multi-stream sorting of cells, and preliminary testing demonstrated that prostate cancer PC3 cells were continuously deflected toward the top of the channel under an electric field, as predicted by the numerical model.
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Barton, Rachael. "Isolation and characterisation of the ovarian cancer antigen CA125 and the development of gene directed enzyme prodrug therapy for the treatment of ovarian cancer." Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275193.
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Jiménez, Sánchez Alejandro. "Characterisation of the tumour microenvironment in ovarian cancer." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/287935.
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The tumour microenvironment comprises the non-cancerous cells present in the tumour mass (fibroblasts, endothelial, and immune cells), as well as signalling molecules and extracellular matrix. Tumour growth, invasion, metastasis, and response to therapy are influenced by the tumour microenvironment. Therefore, characterising the cellular and molecular components of the tumour microenvironment, and understanding how they influence tumour progression, represent a crucial aim for the success of cancer therapies. High-grade serous ovarian cancer provides an excellent opportunity to systematically study the tumour microenvironment due to its clinical presentation of advanced disseminated disease and debulking surgery being standard of care. This thesis first presents a case report of a long-term survivor (>10 years) of metastatic high-grade serous ovarian cancer who exhibited concomitant regression/progression of the metastatic lesions (5 samples). We found that progressing metastases were characterized by immune cell exclusion, whereas regressing metastases were infiltrated by CD8+ and CD4+ T cells. Through a T cell - neoepitope challenge assay we demonstrated that pre- dicted neoepitopes were recognised by the CD8+ T cells obtained from blood drawn from the patient, suggesting that regressing tumours were subjected to immune attack. Immune excluded tumours presented a higher expression of immunosuppressive Wnt signalling, while infiltrated tumours showed a higher expression of the T cell chemoattractant CXCL9 and evidence of immunoediting. These findings suggest that multiple distinct tumour immune microenvironments can co-exist within a single individual and may explain in part the hetero- geneous fates of metastatic lesions often observed in the clinic post-therapy. Second, this thesis explores the prevalence of intra-patient tumour microenvironment het- erogeneity in high-grade serous ovarian cancer at diagnosis (38 samples from 8 patients), as well as the effect of chemotherapy on the tumour microenvironment (80 paired samples from 40 patients). Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumours revealed highly prevalent variability in immune signalling and distinct immune microenvironments co-existing within the same individuals at diagnosis. ConsensusTME, a method that generates consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods that predict immune cell populations using bulk RNA data was developed. ConsensusTME improved accuracy and sensitivity of T cell and leukocyte deconvolutions in ovarian cancer samples. As previously observed in the case report, Wnt signalling expression positively correlated with immune cell exclusion. To evaluate the effect of chemotherapy on the tumour microenvironment, we compared site-matched and site-unmatched tumours before and after neoadjuvant chemotherapy. Site- matched samples showed increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, unlike site-unmatched samples where heterogeneity could not be accounted for. In addition, low levels of immune activation pre-chemotherapy were found to be correlated with immune activation upon chemotherapy treatment. These results cor- roborate that the tumour-immune interface in advanced high-grade serous ovarian cancer is intrinsically heterogeneous, and that chemotherapy induces an immunogenic effect mediated by cytotoxic cells. Finally, the different deconvolution methods were benchmarked along with ConsensusTME in a pan-cancer setting by comparing deconvolution scores to DNA-based purity scores, leukocyte methylation data, and tumour infiltrating lymphocyte counts from image analysis. In so far as it has been benchmarked, unlike the other methods, ConsensusTME performs consistently among the top three methods across cancer-related benchmarks. Additionally, ConsensusTME provides a dynamic and evolvable framework that can integrate newer de- convolution tools and benchmark their performance against itself, thus generating an ever updated version. Overall, this thesis presents a systematic characterisation of the tumour microenvironment of high grade serous ovarian cancer in treatment-naive and chemotherapy treated samples, and puts forward the development of an integrative computational method for the systematic analysis of the tumour microenvironment of different tumour types using bulk RNA data.
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Zampolla, Tiziana. "Development of new methods to assess the quality of zebrafish (Danio rerio) ovarian follicles." Thesis, University of Bedfordshire, 2009. http://hdl.handle.net/10547/134961.
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High quality fish oocytes are essential for in vitro maturation (IVM), in vitro fertilization (IVF) protocols, and for use in cryopreservation. It is important to develop methods for assessing oocyte quality for applications in aquaculture, the preservation of endangered species and managing fish models used in biomedical research. The lack of reliable methods of evaluating oocyte quality limits progress in these areas. The present study was undertaken to develop new methods to assess ovarian follicle viability and quality of stage III zebrafish (Danio rerio) ovarian follicles. The methods developed were then applied to study the impact of cryoprotectant and/or cryopreservation procedures. A vital staining procedure, not previously used with zebrafish oocytes, has been investigated. FDA-PI (Fluorescein diacetate-Propidium Iodide) staining was found to be a more sensitive then currently used viability tests and it could also be applied to all ovarian follicles developmental stages. Mitochondrial activity and distribution as biological markers was investigated with the mitochondrial membrane potentialsensitive dye JC-1- (5,5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine iodide). Confocal microscopy, Cryo-scanning and electron microscopy studies were undertaken to determine mitochondria distributional arrangement within the ovarian follicle. This provided new information on zebrafish ovarian follicle structure, and showed that mitochondria exhibited a contiguous distribution at the margin of the granulosa cell layer surrounding stage III zebrafish oocytes. Cryoscanning results showed a polygonal structure of the vitelline envelope, which is reported here for the first time with the mitochondrial distributional arrangement in the granulosa cell layer. Mitochondrial distribution and the evaluation of mitochondrial activity proved to be sensitive markers for ovarian follicle quality, providing more detailed information on cryoprotectant impact. The measurement of ATP levels, ADP/ATP ratio and mtDNA copy number were also undertaken following cryoprotectant exposure. These findings, together with the observation of mitochondrial distribution, suggested that even cryoprotectant treatments that are considered to have little or no toxicity can have a deleterious effect on mitochondrial activity, potentially compromising oocyte growth and embryo development. Therefore, a further optimization of the currently used protocol may need to be considered. The study of organelle distribution and organisation would support in vitro maturation and oocyte development fields, as well as their use as biological markers for quality determination. These findings will contribute to a better understanding of oogenesis/folliculogenesis processes in fish.
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Flannery, Meghan Maureen. "Development of a Tissue Factor-Targeted Ultrasound Microbubble for Early Detection of Ovarian Cancer." The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1594975031496173.
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Saddick, Salina Yahya. "Effect of the reproductive cycle on morphology and activity of the ovarian surface epithelium in mammals." Thesis, University of Edinburgh, 2010. http://hdl.handle.net/1842/4713.
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The layer of cells lining the outer surface of the mammalian ovary, the ovarian surface epithelium (OSE), is a constant feature throughout the dynamic tissue remodeling that occurs throughout the reproductive cycle (follicle growth, ovulation, corpora lutea formation and pregnancy). Abnormal development of these cells is responsible for 90% of all epithelial ovarian cancers in women and epidemiological studies have shown that susceptibility to ovarian cancer is negatively correlated with increasing pregnancy. Little is known about how OSE cells are affected at each stage of the cycle, so the main aim of this study was to determine how the reproductive cycle affected proliferation and degeneration of OSE cells. This study utilised three animal models each with a different type of reproductive cycle: a mono-ovular seasonal breeder (Sheep), a mono-ovular polyoestrous breeder (Cow) and a poly-ovular non human primate (marmoset) to allow comparisons to be made. Comparison of OSE proliferative activity was made in sheep and marmoset at each stage of the cycle including pregnancy and anoestrous. The bovine model was used to investigate apoptotic cell death. Proliferative activity of somatic cells within the sheep ovary was monitored throughout the reproductive cycle by detection of cell cycle markers PCNA and Ki67 using immunohistochemistry. The pattern of OSE proliferation was correlated with the pattern of follicle development at each stage (sheep and marmoset). During pregnancy cell proliferation was significantly lower in OSE and in granulosa cells, reflecting a suppression of mature follicle development during these stages whereas in cycling animals proliferation was increased. Differences in OSE proliferation were observed in relation to the local underlying tissue environment in both sheep and marmoset. Epithelial cell rupture and regeneration enhanced the hormonal mitogenic action on epithelial cells, which showed highest proliferation over corpora lutea in each animal model. To test the hypothesis that these changes are mediated by hormones or growth factors ovine OSE cells were cultured and proliferative activity monitored after treatment with several factors: fetal calf serum (FCS), follicular fluid from follicles of varying sizes, corpora lutea extracts, recombinant human IGF-1, oestradiol and progesterone. IGF alone was demonstrated to have an affect on increasing proliferation of cultured OSE cells. Levels of FSHr and LHr were monitored by quantitative real- time PCR and it was demonstrated that the concentration of gonadotrophin receptors in OSE, increased prior to and after ovulation, at which time the in vivo OSE proliferation also peaked. The in situ apoptosis index was determined in bovine tissue using TUNEL throughout the regular cycle, and at mid and late-pregnancy stages. The results showed that pregnancy induced apoptotic activity in OSE cells and up regulated the tumour suppressor gene p53. Cultured bovine OSE cells also exhibited an increased level of apoptosis following progesterone treatment. Since p53/p53 gene expression in OSE over the corpora lutea producing progesterone also increased, this progesterone-mediated apoptosis may be mediated through an up-regulation of p53 synthesis. The effect of pregnancy and low production of gonadotrophins in the regulation of OSE cell morphology and activity was further investigated in the marmoset monkey (a non-human primate) treated with GnRH antagonist and infused with BrdU to monitor proliferative activity. OSE proliferation was correlated to ovarian events (follicular growth, ovulation and luteinization) and this was suppressed during pregnancy. Inhibition of gonadotrophin secretion by treatment with a GnRH antagonist also markedly inhibited OSE proliferation. Taken together these studies support the hypothesis that pregnancy and periods of anovulation reduce proliferation of OSE cells and alter the pattern of apoptotic cell death and that this effect is independent of species and reproductive pattern. Suppression of gonadotrophins and other growth factors during pregnancy could enhance p53-mediated apoptosis of damaged and mitogenic cells arising from repeated ovulations. This effect may partly explain why increasing number of pregnancies in woman reduces the chance of epithelial ovarian cancers.