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1
Lo, Belinda. "Investigating follicle development using in vitro technologies." Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:9f646f48-bf7c-426e-a6b0-1d6e8f0f5adc.
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Patients with dysfunctional ovaries, such as those with premature ovarian insufficiency and granulosa cell tumours, do not have normal follicle development and may not respond to traditional assisted reproductive techniques. Using the reaggregated ovary (RO) technique, these patients' oocytes may be reaggregated with functional supporting cells and cultured in vitro to develop fertilisable eggs. However, current research using ROs have only used murine ovaries as a somatic cell source. In this thesis, with the aim of moving towards a clinical treatment, we assessed follicle development in ROs in vitro and progressed to using the technique with human tissues. To assess whether an older murine somatic cell source resulted in advanced follicle development, and how follicle development differed between transplanted and cultured ROs, ROs were generated using postnatal day 2 (P2) and P6 mouse ovaries. To investigate theca cell development in follicles from cultured tissue, mouse ovaries were cultured with mouse serum or encapsulated in hyaluronan hydrogels. Prior to generating and culturing chimeric human-mouse ROs (HuMoROs), competent handling and digestion of bovine cortical tissue was required. Broadly, ROs generated from both P2 and P6 exhibited similar follicle development in vitro after 14 d of culture, and follicles from cultured ROs were more developed than those from transplanted ROs. Theca cell development observed in follicles from cultured ovaries was still poorer than those from in vivo ovaries, even when ovaries were cultured in mouse serum or encapsulated in a hyaluronan hydrogel. Finally, some follicles containing potential human oocytes developed within the generated HuMoROs after 7 d of culture. These results have highlighted the potential of the RO technique as a method to generate fertilisable eggs and identified further aspects which need to be targeted in order to improve the success of the technique.
2
Webber, Lisa Jan. "Prenatal follicle development in normal and polycystic ovaries." Thesis, Imperial College London, 2005. http://hdl.handle.net/10044/1/11954.
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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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Miller, Andrew Thomas. "Control of follicle growth and development in pigs." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387658.
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Ralph, John Hunter. "Factors affecting follicle and oocyte development in cattle." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/11889.
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The mechanisms governing development of mammalian oocytes are not well understood. Isolation and in vitro growth of immature cattle follicles will enable determination of the factors affecting bovine follicular development, have potential applications in assisted reproduction and provide a suitable model for studying human infertility. Intercommunication of the oocyte and somatic cells is necessary for normal oocyte and follicle development. Studies using systems where oocyte-somatic cell communication is preserved allows an accurate assessment of the factors affecting follicular development. The aims of this project were to examine early follicle and oocyte development in cattle and determine whether the bovine oocyte plays a role in follicular development. A non-enzymatic isolation procedure was developed which allowed intact bovine follicles to be isolated. On the basis of follicle size, these could be divided into 3 distinct stages: large preantral, large preantral/early antral and antral follicles. A culture technique was devised which supported in vitro follicle and oocyte development, the key elements of which were: volume of medium (0.25 ml/follicle), serum and insulin minimal number of medium changes and a substrate of collagen. The effect of FSH on preantral to early antral follicles in culture was examined. Initial experiments on large preantral/early antral follicle growth found that all FSH doses stimulated an increase in follicle diameter. The dose of FSH was important as low levels did not stimulate proliferation or affect oocyte size whilst high levels reduced proliferation, inhibited oocyte growth and reduced oocyte quality. Oocyte localised granulosa cell proliferation was observed in some follicles only when a healthy oocyte was present, demonstrating the importance of oocyte-somatic cell communication in granulosa cell proliferation and differentiation. The intensity of oocyte localised proliferation was reduced at high FSH doses, confirming its dose dependent inhibitory effect on follicular development. FSH stimulated the growth of large preantral/early antral and antral follicles but not oocyte growth in any of the stages. The increase in size was due to an increase in intercellular spacing and, as antral cavities were neither maintained or formed during culture, this may be analogous to antrum development. FSH maintained granulosa cell proliferation in all follicle size classes. No detectable effect of FSH on preantral follicles were found, therefore the effect of FSH depends on the stage of follicle examined.
6
Boland, Nicola I. "Experimental investigation of follicle development in mammalian ovaries." Thesis, University of Edinburgh, 1993. http://hdl.handle.net/1842/20104.
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Follicle development in the mouse ovary has been studied using two experimental approaches: firstly, a novel culture system was designed to investigate the metabolism of individual follicles for the first time, and secondly, chimaeric mice and molecular biology techniques were employed to study follicle morphogenesis and the developmental relationships between the different ovarian cell types. Physiological studies of follicle metabolism have been limited by the absence of a suitable culture system which is capable of supporting normal follicle growth and maturation. A novel culture system was developed to provide a physiological model for studies of metabolism by individual mouse ovarian follicles. This system supports the growth of individual primary mouse follicles to Graafian stages <i>in vitro</i> over a period of 5 days and is the first model demonstrating apparently normal ovulation of <i>in vitro</i>-grown follicles in response to LH. Preantral follicles of c.180 microns diameter were micro-dissected from the ovaries of 4 week old mice using fine needles and cultured individually in 20 μl of medium under mineral oil in V-shaped wells of a microtitre plate for a period of 6 days. Medium was supplemented with 1IU/ml hFSH and 5% serum from hypogonadal (<i>hpg/hpg</i>) mice. After every 24 hours of culture, follicles were washed and transferred to wells containing 20 μl of fresh medium: samples of 5-10 μl were then taken from the previous well for the analysis of metabolites. During growth and ovulation in culture, follicles and oocytes were morphologically indistinguishable from those during culture, indicating that premature luteinization does not occur in this system. Approximately 60% of dissected follicles reach preovulatory sizes during culture, which is considerably greater than the maturation rate <i>in vivo</i>, indicating that atresia is not a pre-programmed event. Experiments demonstrated that FSH-stimulation is required for full antral development and LH-induced ovulation, confirming that FSH confers LH-responsiveness to the follicle.
7
Harris, Susan Jane. "Properties of Vibrissa follicle cells during follicle development and regeneration, and their interactions with embryonic stem cells." Thesis, Durham University, 2001. http://etheses.dur.ac.uk/3815/.
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Follicular dermal cells possess properties that regulate induction of follicle formation, hair growth, and follicle end bulb regeneration after amputation. While the molecular basis for these developmental interactions are being uncovered, it is evident that innervation, pigmentation and vascular! sation of the follicle, together with its role as a stem cell repository, make interpretations of molecular function within the follicle, complex. This thesis examined aspects of vibrissa follicle development using immunohistochemistry, and demonstrated that segregation of the follicle dermis and epithelial differentiation were defined by lamin-A antibody. Versican, a proteoglycan recently implicated in dermal papilla induction, was absent from early dermal condensations, but its expression correlated with follicle innervation during development and the adult hair growth cycle. When lower follicle regeneration was studied with in situ hybridisation and immunohistochemistry, versican showed two distinct expression domains. These were the dermal components of the end bulb and the follicle neck. BrdU labelling of cell division showed regeneration of the epithelial component to be consistent with stem cell location. Paucity of dermal cell proliferation left the precise origin of the new dermal papilla unresolved, but a-smooth muscle actin expression showed that dermal sheath cells moved through the glassy membrane. Sonic hedgehog expression indicated that epithelial-mesenchymal interactions, evident in follicle development, were mirrored in regeneration. A co-culture model investigated the capacity of follicular dermal cells to induce embryonic stem (ES) cell differentiation. Unexpectedly, follicle cells were seen to maintain ES cells in an undifferentiated condition. Differentiation assays demonstrated that ES cells remained pluripotent after co-culture, lnterleukin-6 family cytokines, known to maintain ES cell pluripotency, were detected by RT-PCR in cultured cells and vibrissa follicles. Thus, since the follicle dermis produces these cytokines, they may be acting to inhibit the differentiation of follicular epithelial stem cells and/or maintain multipotent stem cell populations in the follicle.
8
Basiouni, Ghazi Faisal. "Preovulatory follicle development and defective luteal function in sheep." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262149.
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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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Miranda, Benjamin H. "Development of a novel, clinically-relevant model for investigating factors that stimulate human hair growth." Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5731.
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Lack of hair due to alopecia or skin grafting procedures causes significant distress due to hair's role in social and sexual communication. Only limited pharmacological agents are currently available to stimulate hair growth; their development is hampered by inappropriate model systems. Most research involves large terminal scalp follicles rather than the clinical targets of tiny vellus or intermediate follicles. The overall aim of this thesis was to develop a novel model system based on intermediate hair follicles. Initially, intermediate follicles from female pre-auricular skin were characterised and compared to matched terminal follicles. Intermediate follicles were smaller, less pigmented, shorter and possessed a more 'tubular' bulb morphology than their more 'bulbous' terminal counterparts. Significant correlations were demonstrated between various hair follicle measurements and corresponding dermal papilla diameters. Isolated terminal follicles grew significantly more than intermediate hair follicles in organ culture for 9 days. Testosterone (10nM), the major regulator of human hair growth, increased only intermediate follicle growth; the anti-androgen, cyproterone acetate (1μM), prevented this stimulation, unlike the 5α-reductase type 2 inhibitor finasteride (40ng/ml). Immunohistochemistry demonstrated androgen receptor and 5α-reductase type 2 proteins in both follicle types, while quantitative real-time PCR and gene microarray analysis detected their increased gene expression in intermediate follicles. Thus, smaller intermediate follicles showed major morphological and gene expression differences to terminal follicles in vivo and retained significant, biologically-relevant differences in vitro in organ culture including androgen-responsiveness. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth.
11
Moore, Anthony G., University of Western Sydney, and School of Science. "The role of the extracellular matrix in wool follicle development." THESIS_XXXX_SS_Moore_A.xml, 1999. http://handle.uws.edu.au:8081/1959.7/389.
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Molecular and behavioural characterisation of ovine dermal papilla cells performed in this study indicate they synthesise a highly specialised extracellular matrix (ECM). This is conserved between different species and distinguishes papilla cells from dermal fibroblasts with which they have a common origin. The composition of the dermal papilla ECM is temporally and spatially regulated during wool follicle development. It was shown that the ECM associated with dermal papilla cells in foetal sheep skin becomes specialised in regard to chondroitin sulphate synthesis prior to the appearance of follicle primordia. Chrondroitin sulphate and fibronectin were present in the ECM of dermal papilla cells throughout follicle development and during fibre production. Cellular differentiation antigen 44 was present in the ECM od papilla cells exclusively during the formation of dermal papilla, while laminin was present in the dermal papilla ECM of fibre producing follicles only. Co-operation between chondroitin sulphate, fibronectin, and CD44 in regulating the agrregative and proliferative behaviour of papilla cells was demonstrated in culture. Finally, the inhibition of proteoglycan synthesis in newborn mouse skin was found to disrupt the growth of existing follicles and the generation of new ones. Together these findings demonstrate that chondroitin sulphate is intimately associated with the earliest interactions between epithelial and mesenchymal cells during the formation of follicle primordia. It is likely that the interactions specifically involve fibronectin and CD44, and possibly other ECM molecules which have he effect of regulating the behaviour of papilla cells<br>Doctor of Philosophy (PhD)
12
Richings, Nadine Maree. "Growth, development and maturation of the marsupial follicle and oocyte /." Connect to thesis, 2004. http://eprints.unimelb.edu.au/archive/00001516.
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Granados-Aparici, Sofia. "TGFβ signalling and cell cycle regulation during early follicle development". Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/18898/.
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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.
15
Wang, Yuan. "Studies of gonadotropin control of inhibin secretion and follicle development." Thesis, The University of Sydney, 2002. https://hdl.handle.net/2123/27898.
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The studies in this thesis were designed to investigate the gonadotropin control
of inhibin secretion, cellular localization, activin action pathway, and follicle
development. A human inhibin assay (ELISA) was validated for the
measurement of inhibins in mouse preparations. It was found that the serial
dilutions of human inhibin standards exhibited a significant deviation from
parallelism to a series of mouse preparations, whereas the different mouse
inhibin preparations appeared to dilute out parallel to each other. The result
suggests that human inhibin standard is not suitable for the inhibin
measurement in mouse samples. Mouse inhibin standards from conditioned
mouse follicle culture medium diluted in castrated male mouse serum were
therefore established for inhibin measurement in mouse serum.
The gonadotropin control of inhibin secretion was investigated by administration
of FSH and hCG to hpg mice in vivo. FSH significantly increased the serum
concentrations of inhibin A and inhibin B, while hCG alone had no stimulating
effect. However, when hCG was given in the presence of FSH, it significantly
increased inhibin A secretion without further effect on inhibin B secretion. The
acute, high dose of hCG to mimic ovulation suppressed the secretion of inhibin A
and inhibin B. These findings suggest that while FSH is important in stimulating
inhibin B production, LH may be more important than FSH in stimulating inhibin A
secretion during follicle maturation. In addition, the LH surge may be responsible
for the decline in inhibin secretion.
16
Moore, Anthony G. "The role of the extracellular matrix in wool follicle development." Thesis, View thesis, 1999. http://handle.uws.edu.au:8081/1959.7/389.
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Molecular and behavioural characterisation of ovine dermal papilla cells performed in this study indicate they synthesise a highly specialised extracellular matrix (ECM). This is conserved between different species and distinguishes papilla cells from dermal fibroblasts with which they have a common origin. The composition of the dermal papilla ECM is temporally and spatially regulated during wool follicle development. It was shown that the ECM associated with dermal papilla cells in foetal sheep skin becomes specialised in regard to chondroitin sulphate synthesis prior to the appearance of follicle primordia. Chrondroitin sulphate and fibronectin were present in the ECM of dermal papilla cells throughout follicle development and during fibre production. Cellular differentiation antigen 44 was present in the ECM od papilla cells exclusively during the formation of dermal papilla, while laminin was present in the dermal papilla ECM of fibre producing follicles only. Co-operation between chondroitin sulphate, fibronectin, and CD44 in regulating the agrregative and proliferative behaviour of papilla cells was demonstrated in culture. Finally, the inhibition of proteoglycan synthesis in newborn mouse skin was found to disrupt the growth of existing follicles and the generation of new ones. Together these findings demonstrate that chondroitin sulphate is intimately associated with the earliest interactions between epithelial and mesenchymal cells during the formation of follicle primordia. It is likely that the interactions specifically involve fibronectin and CD44, and possibly other ECM molecules which have he effect of regulating the behaviour of papilla cells
17
Moore, Anthony G. "The role of the extracellular matrix in wool follicle development /." View thesis, 1999. http://library.uws.edu.au/adt-NUWS/public/adt-NUWS20030901.152349/index.html.
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Thesis (Ph.D) -- University of Western Sydney, Nepean, 1999.<br>Thesis submitted for degree of Doctor of Philosophy, University of Western Sydney, Nepean and CSIRO Division of Animal Production. Includes bibliographical references.
18
Atess, Victoria. "Growth factor regulation of preantral follicle development in the mouse ovary." Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/44959.
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At, or around, birth female mammals are already endowed with a finite stock of oocytes. The majority are housed within non-growing primordial follicles but, from birth until depletion, a steady trickle initiate growth. The regulation of this process is poorly understood, despite its importance in defining reproductive lifespan. Primordial activation is characterised by oocyte growth, granulosa cell (GC) cuboidalisation and proliferation. N-cadherin is the major cell adhesion molecule (CAM) associated with GC cuboidalisation in mouse. CAMs are known to associate and signal with receptor tyrosine kinases (RTKs). Several RTKs have been implicated in regulating primordial activation and have been localised to GCs. Therefore, we hypothesised that RTKs may regulate primordial activation via interaction with N-cadherin in mouse. Association of candidate RTKs with N-cadherin was assessed by immunofluorescence. ErbB2, an RTK member of the Epidermal growth factor (EGF) family, which relies on heterodimerisation to signal co-localised with N-cadherin in cuboidalising GCs. Furthermore, expression of a downstream anti-proliferative protein, transducer of ErbB2 (TOB1), provides evidence that ErbB2 may regulate the onset of GC proliferation during primordial activation. A suitable antibody was not available to identify a dimer partner, but PCR demonstrated that Egfr and ErbB3 expression. The sensitivity of isolated preantral follicles to EGF, which stimulated follicle growth, and inhibitors to EGFR, which blocked EGF-stimulated follicle growth, demonstrate that EGFR is expressed and available to dimerise with ErbB2 and also provides strong evidence that EGFR signalling is important in preantral GC proliferation. Crucially, culture of whole d4 ovaries in either EGF of Lapatinib, an inhibitor of EGFR/ErbB2 provide evidence to suggest that these proteins regulate mouse primordial activation.
19
Hester, Mark. "Utilization of gene knockout approaches in the mouse to elucidate additional functions of smad proteins during mammalian development." The Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1118656704.
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Viñoles, Gil Carolina. "Effect of nutrition on follicle development and ovulation rate in the ewe /." Uppsala : Dept. of Clinical Chemistry, Swedish Univ. of Agricultural Sciences, 2003. http://epsilon.slu.se/v165.pdf.
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McFee, Renee Marie. "The role of vascular endothelial growth factor isoforms in early follicle development." Thesis, Kansas State University, 2012. http://hdl.handle.net/2097/13525.
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Master of Science<br>Department of Animal Sciences and Industry<br>Timothy G. Rozell<br>Since vascularization of the theca layer increases as follicles progress in size through preantral and antral stages, the principal angiogenic factor, vascular endothelial growth factor A (VEGFA), may influence follicle growth via regulation of angiogenesis. However, VEGFA may also influence follicular development through nonangiogenic mechanisms since its expression has been localized to nonvascular follicles and cells. Alternative mRNA splicing of 8 exons from the VEGFA gene results in the formation of different VEGFA isoforms. Each isoform has unique properties and is identified by the number of amino acids within the mature protein. Proangiogenic isoforms are encoded by exon 8a while a sister set of isoforms with antiangiogenic properties are encoded by exon 8b. The antiangiogenic isoforms comprise the majority of VEGFA expressed in most tissues while expression of the proangiogenic VEGFA isoforms is upregulated in tissues undergoing active angiogenesis. The Vegfa angiogenic isoforms (Vegfa_120, Vegfa_164, and Vegfa_188) were detected in developing rat ovaries, and quantitative RT-PCR determined that Vegfa_120 and Vegfa_164 mRNA was more abundant after birth, while Vegfa_188 mRNA was highest at embryonic day 16. The antiangiogenic isoforms, Vegfa_165b and Vegfa_189b, were amplified and sequenced from rat ovaries and quantitative RT-PCR determined that Vegfa_165b mRNA was more abundant around embryonic day 18, but Vegfa_189b lacked a distinct pattern of abundance. VEGFA and its receptors were localized to pregranulosa and granulosa cells of all follicle stages and to theca cells of advanced-stage follicles. Antiangiogenic VEGFA isoforms were localized to pregranulosa and granulosa cells of all follicle stages and to theca cells of advanced-stage follicles. To determine the role of VEGFA in developing ovaries, postnatal day 3/4 rat ovaries were cultured with VEGFR-TKI, a tyrosine kinase inhibitor that blocks signaling through the VEGFA receptors, FLT1 and KDR. Ovaries treated with VEGFR-TKI had vascular development reduced by 94%. In addition, treated ovaries had more primordial follicles, fewer early primary, transitional, and secondary follicles, and greater total follicle numbers compared with control ovaries. This suggests that VEGFA promotes follicle recruitment and early follicular development. These effects may be dependent upon increased ovarian vascularization or they may be mediated by nonvascular mechanisms.
22
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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Sharum, Isam. "Regulation of TGFβ/Smad signalling during early follicle development in the mouse ovary". Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/15990/.
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The molecular events responsible for the activation and growth of gonadotropin-independent stages of follicles are not well understood. This study is interested on the role of TGFβ signalling based on preliminary findings from our laboratory suggesting that this pathway is important in this context. Specifically, nuclear expression of the TGFβ signalling mediators and transcription factor Smad2/3 were more evident in the granulosa cells of primordial follicles but appeared to be excluded from nuclei in cells of early growing follicles. The overall aim of this thesis was to identify factors that have the potential to inhibit the Smad2/3 pathway and potentially determine their impact on early follicle development in the mouse ovary. Therefore, the first part of the study evaluated the expression of a selected of candidate genes (known to inhibit Smad signalling) during early follicle development. Many Smad inhibitors were detectable, although serine-threonine kinase receptor associated protein Strap was further evaluated as its protein expression in granulosa cells of small follicles coincided with Smad2/3 staining. Neonatal mouse ovary fragments and preantral follicle culture models were employed to evaluate the function of Strap. Inhibition of Strap caused a significant reduction in the proportion of primordial follicles, leading to an increase in the proportion and size of growing follicles, while Strap supplementation promoted the growth of preantral follicles. Therefore, it is indicated that Strap can regulate the early follicle development in a stage-dependent manner and its function can be employed to expand our knowledge regarding several reproductive disorders, such as premature ovarian failure. The expression of another Smad inhibitor, Tmepai, was also assessed and was found to be specifically localised in small preantral follicles that had just initiated growth. Since this coincided with the aforementioned reduction in nuclear Smad2/3, attempts were then made to determine whether TGFβ signalling regulated its expression. Inhibition of TGFβRI in cultured preantral follicles caused a significant decrease in Tmepai expression level. Thus, it is suggested that Tmepai can regulate TGFβ signalling in a negative feedback mechanism and consequently a relevant role in follicle growth. Finally, considering that TGFβ requires processing for their activity, and considering the evidence in this thesis and elsewhere that TGFβ signalling is important throughout the early stages of follicle development, we looked at the expression of the latent TGFβ binding proteins (Ltbp) in mouse ovaries. Transcripts of Ltbp1-4 were expressed in the immature and adult ovaries. Ltbp1 protein appeared to be more evident in the ovary surface, while Ltbp4 mainly detected in blood vessels. These distinct expression patterns might indicate that each Ltbp member functions in a diverse way. In conclusion, this thesis presents a series of studies that show the essential role of TGFβ/Smad2/3 signalling in the regulation of early follicle development in the mouse ovary. The expression of many Smad2/3 inhibitors indicates that Smad pathway is regulated by a complex mechanism. Strap can regulate early follicle growth in a stage-specific manner. Tmepai is detectable in follicles with specific growth stages and regulated through TGFβRI receptor. The extracellular modulator of TGFβ ligands (Ltbp1-4) are expressed in the ovary, where their relative proteins localised in distinct compartments of the ovary.
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Fouladi, Nashta Ali Akbar. "Follicle oocyte interactions and embryo development in the bovine : an in vitro study." Thesis, University of Edinburgh, 1999. http://hdl.handle.net/1842/29765.
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In systems currently employed for the production of bovine embryos <I>in vitro</I>, the frequency of development to the blastocyst stage and subsequently production of live offspring is lower than that observed <I>in vivo</I>. Typically for <I>in vitro</I> maturation and fertilization oocytes are aspirated from a wide range of follicle sizes (2-8 mm in diameter). Oocytes increase in size with enlargement of the follicles, and those from larger follicles have a higher developmental competence. This suggests that oocytes from small antral follicles may be deficient in some vital factor/s which are important for embryonic development. <I>In vivo</I>, oocytes remain arrested at the germinal vesicle (GV) stage until hormonally stimulated. In contrast, when aspirated from follicles <I>in vitro</I>, they are released from the inhibitory function/s of the follicle wall and develop to the second metaphase (MII) stage. It was hypothesised that if oocytes are cultured <I>in vitro</I> in conditions which maintain GV arrest, then the oocyte may have the opportunity to synthesise or modify factors which are required for embryonic development. A culture system was established in which intact large antral follicles of 4-8 mm in diameter remained viable for up to 7 days. The majority of oocytes (96.8%) recovered following 24 hours of follicle culture remained arrested at the GV stage. On removal from the follicle and transfer to a suitable medium, 80% of these oocytes resumed meiosis and developed to the MII stage. However, with increasing periods of follicle culture, both the number of GV arrested and MII matured oocytes was significantly reduced. Follicle culture for a period of 24 hours was used for the all subsequent experiments. Follicle culture derived oocytes resulted in a significantly higher rate of blastocyst production than directly aspirated oocytes.
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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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Jagarlamudi, Krishna Rao. "The functional roles of the intra-oocyte phosphatidylinositol 3-kinase (PI3K) signaling in controlling follicular development in mice." Doctoral thesis, Umeå : Umeå university, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-26110.
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Alam, Majid Ali. "Investigation of regulatory functions of microRNAs in skin and hair follicle development and cycling : a role of microRNA-214 in skin and hair follicle homeostasis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/6481.
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miRNAs are important post-transcriptional regulators of gene expression which play vital roles in the arrays of physiological processes, including skin and hair follicle (HF) development. In this study, the role for miR-214 in the skin and HF development and their postnatal physiological regeneration was investigated. miR-214 exhibits discrete expression patterns in the epidermis and HF in developing and postnatal skin, and is highly expressed in the epithelial stem cells and their lineage-committed progenies. The effects of miR-214 on HF morphogenesis and cycle progression were evaluated by using doxycyclineinducible miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte specific miR-214 overexpression during skin embryogenesis resulted in the partial inhibition of HF induction and formation of the HF reduced in size producing thinner hair. Overexpression of miR-214 in telogen skin caused retardation of the anagen progression and HF growth. Inhibitory effects of miR- 214 on HF development and cycling were associated with supressed activity of stem cells, reduced proliferation in the hair matrix, and altered differentiation. miR-214 induced complex changes in gene expression programs in keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas β-catenin acts as a novel conserved miR-214 target. Indeed, the inhibitory effects of miR-214 on HF development were rescued by intracutaneous delivery of pharmacological Wnt activator. Thus, this study demonstrated that by targeting β-catenin and, therefore, interfering with Wnt signalling activity miR-214 may act as one of the upstream effectors of the signalling cascades which govern HF morphogenesis and cycling.
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Alam, Majid A. "Investigation of regulatory functions of micrornas in skin and hair follicle development and cycling. A role of microRNA-214 in skin and hair follicle homeostasis." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/6481.
Full textAbstract:
miRNAs are important post-transcriptional regulators of gene expression which
play vital roles in the arrays of physiological processes, including skin and hair
follicle (HF) development. In this study, the role for miR-214 in the skin and HF
development and their postnatal physiological regeneration was investigated.
miR-214 exhibits discrete expression patterns in the epidermis and HF in
developing and postnatal skin, and is highly expressed in the epithelial stem
cells and their lineage-committed progenies. The effects of miR-214 on HF
morphogenesis and cycle progression were evaluated by using doxycyclineinducible
miR-214 transgenic mice (K14-rtTA/TRE-miR-214). Keratinocyte
specific miR-214 overexpression during skin embryogenesis resulted in the
partial inhibition of HF induction and formation of the HF reduced in size
producing thinner hair. Overexpression of miR-214 in telogen skin caused
retardation of the anagen progression and HF growth. Inhibitory effects of miR-
214 on HF development and cycling were associated with supressed activity of
stem cells, reduced proliferation in the hair matrix, and altered differentiation.
miR-214 induced complex changes in gene expression programs in
keratinocytes, including inhibition of cyclins and cyclin-dependent kinases and
several essential components of Wnt, Edar, Shh and Bmp signalling pathways, whereas -catenin acts as a novel conserved miR-214 target. Indeed, the
inhibitory effects of miR-214 on HF development were rescued by
intracutaneous delivery of pharmacological Wnt activator.
Thus, this study demonstrated that by targeting -catenin and, therefore,
interfering with Wnt signalling activity miR-214 may act as one of the upstream
effectors of the signalling cascades which govern HF morphogenesis and
cycling.
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Spence, Susan Claire. "Exploring the role of the phosphatidylinositol-3'-kinase (PI3K) pathway in primordial follicle activation and subsequent development." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23659.
Full textAbstract:
Mammalian females form their germ cells (oocytes) before or shortly after birth. The oocytes interact with somatic cells to form primordial follicles, creating the quiescent population from which oocytes will be recruited to grow throughout life. A female’s fertility life span is therefore, dependant on the size of this pool and the rate at which primordial follicle are activated to grow. However, there is still much we do not know about the quiescent follicle population and the mechanisms that control their recruitment into the growing follicle population are still unclear. There is evidence that the phosphoinositide-3-kinase (PI3K) pathway is key to activation of follicle growth. The role of the PI3K pathway has been primarily explored in the rodent model and has highlighted this pathway’s importance both in the activation of quiescent follicle growth and maintaining dormancy of the quiescent follicle population. This thesis aimed to explore if the PI3K pathway played a similar role in a large mono-ovulatory species as it does in the small polyovulatory rodent species. Bovine is a mono-ovulate species, which has similar attributes in its reproduction and folliculogenesis to the human in vivo; therefore using an in vitro bovine model might be a valuable indication of the role of the PI3K pathway in the human. Initial experiments tested if the bovine was a good model for human primordial follicle activation in an in vitro environment. It was observed that the bovine and human had comparative levels of activation and subsequent increases in both the primary and secondary follicle populations within an in vitro culture system. These similarities indicate that the bovine is a relevant model for the human in vitro. It is not possible to culture the entire bovine ovary. Therefore knowing the location of the primordial follicles is important to establishing what region(s) of the ovary to use. The overall concentration of ovarian follicles was higher in the cortex and gradually declined through the consecutive inner layers of the ovary. The distribution of the ovarian follicle populations were different in each distinctive region of the ovary with the quiescent follicles representing a much larger proportion of the ovarian follicle population in the cortex compared to the inner regions of the ovary. The location an ovarian follicle in the ovary was seen to influence its health in both the quiescent and growing follicle populations, with reduced health seen in the IV inner layers of the ovary compared to the cortex. This resulted in very few healthy quiescent follicles outside of the cortex region making it the more favourable region to culture in functional studies. The role of the PI3K pathway was therefore explored using an in vitro bovine model using the pharmacological compounds bpV (HOpic) and 740Y-P, both of which caused an up-regulation of the PI3K-pathway. It was observed that up-regulation of the PI3K pathway caused an increase in the activation of the quiescent follicle population, and the resulting primary follicles were larger in size. However, there was reduced health in both the growing and quiescent follicle populations. The ill health appears to be due to a disruption in the co-ordination of growth between oocyte and granulosa cells in the ovarian follicles, leading to enlarged oocytes in both the primary follicles and quiescent follicles. Although the PI3K pathway caused an increase in quiescent follicle activation and larger primary follicles there was no increase in the number of viable large secondary follicles obtained. The growth of the secondary follicles was unaltered by the initial activation of the quiescent follicles via the PI3K pathway. These experiments show that the PI3K pathway plays a role in primordial follicle activation in large mono-ovulate species. However, up-regulating the PI3K pathway results in a decrease in health of the quiescent and primary follicle populations, thus limiting its immediate value as a therapeutic target. This study has improved our understanding of the role of the PI3K pathway in primordial follicle activation in a large mono-ovulate species. It has highlighted that the up-regulation of the PI3K pathway using both bpV (HOpic) and 740Y-P increases the activation of the bovine ovarian follicles in vitro. However, up-regulating the PI3K pathway disrupts the development of the ovarian follicles resulting in retarded growth and thereby a decrease in the survival of both the quiescent and growing follicle populations. The similarities in activation, growth and development between the bovine and the human in vitro indicate that the results observed in the bovine are a good indication of what would occur in the human. This study has also improved our understanding of the location, distribution and viability of the ovarian follicle population within the ovary.
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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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Wong, Sze-yin Shirley. "Single nucleotide polymorphism in follicle stimulating hormone receptor and the development of endometrial carcinoma." Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/hkuto/record/B31971349.
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Watson, Elaine A. "The influence of germ cell-specific Dazl on follicle growth and development in mice." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/25290.
Full textAbstract:
The DAZ (Deleted in Azoospermia) gene is located on the human Y chromosome and is associated with male infertility in humans. An autosomal form of this gene (DAZ-like (Dazl)) is present in all mammals and is expressed in germ cells, the Dazl itself being an RNA binding protein. Transgenic homozygous Dazl knockout (KO) male and female mice are infertile due to loss of almost all germ cells in early neonatal life. However, in heterozygous (het) females there is a significant increase in ovulation rate and litter size in comparison to their homozygous wild type (wt) littermates, in spite of lower levels of plasma Follicle Stimulating Hormone (FSH), suggesting an alteration in follicle senstiviity to FSH. The aims of this study were to assess follicle numbers in ovaries and follicle FSH-sensitivity in het mice compared to wt mice. The present studies suggest that, although Dazl is an oocyte-specific gene, the putative protein(s) that Dazl affects through RNA binding in the oocyte targets granulosa cells. The influence of Dazl on follicle development occurs through the single copy of Dazl enhancing FSH sensitivity, but the exact mechanism of Dazl on the granulosa cells is unknown. The studies presented in this thesis suggest that follicles from the Dazl het mice have accelerated growth because of a reduced threshold for FSH that allows them to remain for a longer duration within the critical FSH threshold for follicle growth. In addition, this study suggests that the percentage of healthy and atretic follicles in the Dazl wt and het mice is similar in untreated and oFF-treated mice, but that after FSH treatment there are more healthy follicles in het mice. It could be concluded that, in the adult after follicle activation and recruitment into the pool of growing follicles, a single copy of Dazl results in maintained follicle growth, because of increased FSH-sensitivity. Thus, more larger follicles achieve dominance and these subsequently ovulate, leading to an increased litter size.
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Wong, Sze-yin Shirley, and 黃思賢. "Single nucleotide polymorphism in follicle stimulating hormone receptor and the development of endometrial carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31971349.
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Mitchell, Leila Maria. "The role of nitric oxide in mouse follicle development, survival and ovulation in vitro." Thesis, University of Warwick, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365244.
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Sasway, Hope Marie. "Endothelin-1 gene expression in the porcine ovary follicular development /." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1398.
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Thesis (M.S.)--West Virginia University, 2000.<br>Title from document title page. Document formatted into pages; contains v, 60 p. : ill. (some col.) Includes abstract. Includes bibliographical references (p. [54]-60).
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Liperis, Georgios. "The function of gametocyte specific factor 1 (GTSF1) in mammalian oocyte and ovarian follicle development." Thesis, University of Leeds, 2013. http://etheses.whiterose.ac.uk/6895/.
Full textAbstract:
A detailed understanding of the genes and mechanisms that regulate oocyte growth and maturation underpins the development of improved methods of assisted conception. Gametocyte specific factor 1 (GTSF1)-a putative marker of gamete developmental competence, is highly conserved across species but in mammals demonstrates a sexual dimorphism in its function. In mice, male mutants for Gtsf1 have an infertile phenotype, whereas female mutants appear to have normal ovarian function. It is hypothesised that GTSF1 regulates oocyte development in monovular species such as the sheep. Initial studies characterised the expression and cellular distribution of GTSF1 across cDNA libraries spanning ovine oogenesis and embryogenesis and by using in situ hybridisation of fixed tissue. GTSF1 expression was confined to gonadal and embryonic tissues with highest expression in the ooplasm of germinal vesicle (GV)-staged secondary oocytes. The gene sequence of GTSF1 was obtained and the gene and predicted protein sequences revealed close homology across many species with two conserved CHHC zinc finger domains known to bind RNA. Functional analysis of the role of GTSF1 during sheep oocyte maturation was conducted using short interference RNA (siRNA injection) in conjunction with oocyte in vitro maturation (IVM) and oocytectomised cumulus shell co-culture. This system was validated using siRNA knockdown (kd) for a known oocyte-specific gene, Growth differentiation factor 9 (GDF9). The effect on GTSF1 kd was evaluated following the microinjection of 770 GV oocytes with siRNA target against the sixth exon of ovine GTSF1. The effects of GTSF1 kd were evaluated in 57 MII oocytes and cumulus shells. Targeted kd of GTSF1 in GV oocytes followed by IVM and cumulus shell co-culture did not affect oocyte meiotic progression or cumulus expansion. Microarray analysis using the bovine GeneChip Affymetrix array revealed that 6 down-regulated genes (TCOF1, RPS8, CACNA1D, SREK1IP1, TIMP1, MYL9) following the GTSF1 kd were associated with developmental competence, RNA storage, post-transcriptional modifications and translation. Immunofluorescent studies localized GTSF1 protein to the P-body in GV ovine oocytes. Collectively these results suggest a possible role of GTSF1 in post-transcriptional control of RNA processing, translational regulation and RNA storage which may impact on oocyte developmental competence.
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Maze, Timothy D. "Development of the induced gonadotropin surge mechanism in the prepubertal heifer." Morgantown, W. Va. : [West Virginia University Libraries], 2002. http://etd.wvu.edu/templates/showETD.cfm?recnum=2525.
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Thesis (Ph. D.)--West Virginia University, 2002.<br>Title from document title page. Document formatted into pages; contains viii, 71 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 61-70).
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Papademetriou, Suzanne Andrea. "Role of the SHP-1 tyrosine phosphatase in the regulation of oocyte growth and follicle development." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6300.
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The tyrosine kinase Kit is expressed in oocytes and is involved in primordial germ cell (PGC) proliferation and oocyte growth. Our goal was to determine the involvement of the SHP-1 phosphatase in regulating PGC proliferation and oocyte growth by examining SHP-1 deficient motheaten mice. Ovaries from wild-type and motheaten mice were observed at 10--13 days of age and after transplantation under the kidney capsule of SCID mice. Ovaries were analyzed by histological and western analyses. SHP-1 was expressed in all ovarian cell types throughout follicle development. At 10--13 days, motheaten animals had smaller ovaries, increased numbers of PGCs and decreased granulosa cell proliferation compared to controls. After transplantation, both groups had formed large antral follicles in similar proportions. Interestingly, motheaten oocytes achieved larger sizes than controls. These results suggest that SHP-1 may interact with Kit to regulate PGC proliferation and oocyte growth, however, the loss of SHP-1 does not impair granulosa cell proliferation and follicle development.
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Lim, Teck Por. "Mathematical modelling of the dynamics of ovarian follicle development in the mouse and in the human." Thesis, Imperial College London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590033.
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The ovary is the female reproductive organ where the egg cells are stored, and where hormones are produced. A follicle is a cell aggregation in the ovary which consists of an egg (oocyte) and supporting cells. Throughout the life of each woman, follicles initiate growth, moving from the primordial stage to the primary stage. Subsequently they move to the secondary stage, and then to the tertiary stage. Consequently an understanding of the mechanisms of initiation and development of follicles is of fundamental importance. It may also be helpful to the many women in which the process does not proceed properly; this may be useful for the treatment of infertility in females, and also the in vitro maturation of follicles. The main contribution of this thesis is in the discovery of novel scaling relationships in the human and in the mouse, between primordial follicles and growing follicles. These scaling relationships suggest that the number of follicles entering the growing pool is not constant over time, and yet they also suggest that the proportion of growing follicles to primordial follicles increases as age Increases. ODE models are used in this work; they are models comprising Ordinary Differential Equations, which are equations containing functions of one independent variable (in this case, time) and derivatives of these functions. The scaling relationships are used to simplify ODE models of the dynamics of initiation and atresia (degeneration). A relationship between the rate of initiation and the rate of atresia is predicted. Furthermore. interesting biological questions can be asked. If initiation is controlled by signals (hormones, growth factors, etc), are they the same throughout life, or is there evidence for different mechanisms in the mature adult, and prior to the menopause?
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Nemade, Rashmi Vithal. "THE DISRUPTION OF THE BLOOD FOLLICLE BARRIER IN OVARIAN FOLLICULAR CYST DEVELOPMENT: REGULATION BY NITRIC OXIDE." University of Cincinnati / OhioLINK, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=ucin976039111.
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Leung, Man Ching. "Identification of human hair follicle antigens targeted in the presumptive autoimmune hair follicle disorder Alopecia Areata and their potential functional relevance In Vitro. Methods development for isolation and identification of Alopecia Areata-relevant human hair follicle antigens using a proteomics approach and their functional assessment using an Ex Vivo hair follicle organ culture model." Thesis, University of Bradford, 2008. http://hdl.handle.net/10454/4330.
Full textAbstract:
Alopecia areata (AA) is a putative autoimmune hair loss disorder. It mainly affects the scalp hair but can also involve body hair, and can also affect the nail and the eye. While there are may be several lines of evidence to support the autoimmune basis of AA, there is still very little information on the hair follicle autoantigen(s) involved in its pathogenesis. In this project, serum antibodies (AA=10, control=10) were used to immunoprecipitate AA-relevant target antigens from normal human scalp hair follicle extracts. These immunoprecipitates were analysed by LC-MALDI-TOF/TOF mass spectrometry for target protein identification. This part of the project involved substantial methods development. Trichohyalin was immunoprecipitated by all AA sera, but by only 5 normal sera. Importantly, the mean Mascot scores of the AA group was significantly higher than the normal group (p=0.005). Keratin 16 was also identified from immunoprecipitates as another potential AA-relevant target antigen. Functional studies by ex vivo whole hair follicle organ culture using commercial antibodies to trichohyalin and keratin 16 significantly inhibited hair fibre elongation compared to controls. Indirect immunofluorescence studies revealed that AA sera contained higher immunoreactivity against normal human scalp anagen hair follicles compared to normal sera. Immunoreactivities were mainly in the outer root sheath and inner root sheath, and less so to the medulla and hair bulb matrix. Double immunofluorescence studies of AA and normal serum with anti-trichohyalin antibody (AE15) revealed co-localisation of 9 of the AA sera antibodies with trichohyalin in the inner root sheath (mostly in Henle's, less in Huxley's/inner root sheath cuticle), but only weakly in 3 normal sera. This study supports the involvement of an antibody response to anagen-specific hair follicles antigens in AA. Moreover, there may be some evidence that these antibodies may have a pathogenic role.
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Adhikari, Deepak. "Signaling pathways in the development of female germ cells." Doctoral thesis, Umeå universitet, Institutionen för medicinsk kemi och biofysik, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-88309.
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Primordial follicles are the first small follicles to appear in the mammalian ovary. Women are born with a fixed number of primordial follicles in the ovaries. Once formed, the pool of primordial follicles serves as a source of developing follicles and oocytes. The first aim of this thesis was to investigate the functional role of the intra-oocyte signaling pathways, especially the phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) pathways in the regulation of primordial follicle activation and survival. We found that a primordial follicle remains dormant when the PI3K and mTORC1 signaling in its oocyte is activated to an appropriate level, which is just sufficient to maintain its survival, but not sufficient for its growth initiation. Hyperactivation of either of these signaling pathways causes global activation of the entire pool of primordial follicles leading to the exhaustion of all the follicles in young adulthood in mice. Mammalian oocytes, while growing within the follicles, remain arrested at prophase I of meiosis. Oocytes within the fully-grown antral follicles resume meiosis upon a preovulatory surge of leutinizing hormone (LH), which indicates that LH mediates the resumption of meiosis. The prophase I arrest in the follicle-enclosed oocyte is the result of low maturation promoting factor (MPF) activity, and resumption of meiosis upon the arrival of hormonal signals is mediated by activation of MPF. MPF is a complex of cyclin dependent kinase 1 (Cdk1) and cyclin B1, which is essential and sufficient for entry into mitosis. Although much of the mitotic cell cycle machinery is shared during meiosis, lack of Cdk2 in mice leads to a postnatal loss of all oocytes, indicating that Cdk2 is important for oocyte survival, and probably oocyte meiosis also. There have been conflicting results earlier about the role of Cdk2 in metaphase II arrest of Xenopus oocytes. Thus the second aim of the thesis was to identify the specific Cdk that is essential for mouse oocyte meiotic maturation. We generated mouse models with oocytespecific deletion of Cdk1 or Cdk2 and studied the specific requirements of Cdk1 and Cdk2 during resumption of oocyte meiosis. We found that only Cdk1 is essential and sufficient for the oocyte meiotic maturation. Cdk1 does not only phosphorylate the meiotic phosphoproteins during meiosis resumption but also phosphorylates and suppresses the downstream protein phosphatase 1, which is essential for protecting the Cdk1 substrates from dephosphorylation.
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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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Seppinen, L. (Lotta). "The roles of collagen XVIII and its endostatin domain in wound healing, hair follicle cycling and bone development." Doctoral thesis, University of Oulu, 2009. http://urn.fi/urn:isbn:9789514260643.
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Abstract
Collagen XVIII is a basement membrane proteoglycan, which has three variant N-termini. These variants are coded by two promoters; promoter 1 directs the synthesis of a short variant and promoter 2 directs the synthesis of two longer variants, of which the middle variant is generated from the longest by splicing. The longest variant contains a cysteine-rich domain in its N-terminus, which shows homology to the frizzled receptors of the Wnt molecules and can inhibit Wnt/beta-catenin signalling in vitro. The C-terminal domain of collagen XVIII, endostatin, is an inhibitor of tumor growth and angiogenesis.
Lack of collagen XVIII accelerates cutanous wound healing and wound angiogenesis. Overexpression of endostatin leads to delayed wound healing and the presence of morphologically abnormal wound capillaries. Moreover, endostatin overexpression leads to delayed formation of the wound epidermal basement membrane and impaired maturation of hemidesmosomes.
Endostatin treatment decreases osteoblast proliferation in vitro. Moreover, osteoblast proliferation and mineralization of the matrix by osteoblasts are inhibited when cells are treated with endostatin together with VEGF. In vivo, lack of collagen XVIII leads to delayed formation of secondary ossification centers in mouse femurs, whereas overexpression of endostatin leads to a slower growth of bone length. However, both of these changes are transient and mild, suggesting that collagen XVIII/endostatin is not essential for skeletal development.
The growth of hair follicles is delayed in the mice overexpressing endostatin. This delay in growth is preceded by an impaired hair follicle associated angiogenesis. Lack of collagen XVIII causes an accelerated onset of the first hair cycle. A similar change can be seen in mice lacking the long variants of collagen XVIII. Lack of the short variant causes mild acceleration in the catagen of the first cycle, and anagen is also significantly accelerated in these mice. The long variants were located in the bulge region, which contains the hair follicle stem cells, and in the basement membrane surrounding the dermal papilla. As it is known that several Wnt-inhibitors are upregulated in the bulge, our results suggest that the longest variant of collagen XVIII may have a role as a regulator of Wnt-signalling in hair follicles.
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Buscone, Serena. "Unravelling novel molecular targets for photobiomodulation in human hair follicle towards the development of more effective light-based therapies for hair growth." Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/16001.
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Light and optical techniques have made a profound impact on modern medicine both in diagnostics and in therapy. Therapeutic action of light is based on photomechanical, photothermal, photochemical and photobiological interactions, depending on the wavelength, power density, exposure time and optical properties of tissue and cells. Last decade experienced a growing rise of commercial devices for management of hair growth, where all of them are based on low levels of light resulting into photobiological, non-thermal interaction of photons with cells, a process that recently has received an official term ‘photobiomodulation’. However, the design and analysis of the reported clinical studies are highly debated in a wider scientific community. The picture is further complicated by a virtual lack of proof about the exact molecular targets that mediate the physiological response of skin and hair follicles (HF) to low levels of light. The goal of this project was to investigate the expression of light-sensitive receptors in the human HF and to study the impact of UV-free blue light on hair growth ex vivo. The expression of Cryptochromes 1 and 2 (CRY1, 2), Opsin 2 and 3 (OPN2 and OPN3), but not other Opsins 1, 4 and 5 was detected in the distinct compartments of skin and anagen HF. Evaluation of the physiological role of detected light-sensitive receptors on hair growth was performed by the modulation of photoreceptors activity in HF ex vivo model. HFs treated with KL001, a stabilizer of CRY1 protein that lengthens the circadian period, delayed HF anagen-catagen transition; while silencing of CRY1 induced premature catagen development accompanied by reduced cell proliferation. Silencing of CRY1 in the HF outer root sheath (ORS) cells in vitro caused downregulation of ii genes involved in the control of proliferation; including the cyclin dependent kinase 6 (CDK6). OPN3 also had a positive effect on metabolic activity and proliferation of the ORS cells in vitro. OPN3 silencing resulted in the altered expression of genes involved in the control of proliferation and apoptosis. Investigated CRY1, OPN2 and 3 greatly absorb in the blue to green-region of the visible spectrum. This led us to investigate the effect of blue light on HF growth. Daily treatment with blue light (453 nm, 3.2 J/cm2, 16 nm full width half maximum) prolonged anagen phase in HF ex vivo that was associated with sustained proliferation. In addition, blue light (3.2 J/cm2) significantly stimulated proliferation of ORS cells in vitro. This effect was abrogated by silencing of OPN3. To summarize, CRY 1, OPN 2 and OPN 3 are expressed in the distinct compartments of the HF, including HF stem cells. Blue light (453 nm) at low radiant exposure exerts a positive effect on hair growth ex vivo, potentially via interaction with OPN3. The further research should be conducted to decipher interactions between blue light and the investigated receptors in the HFs. In addition, the beneficial effect of blue light at low radiant exposure on hair growth raises a possibility of increasing therapeutic efficacy when combined with topical chemistry used for management of hair growth.
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Wang, Yifang. "Role and regulation of X-linked inhibitor of apoptosis protein expression during development of the rat ovarian follicle in vitro." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/29006.
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Follicle stimulating hormone (FSH) is an important survival factor in the ovarian follicular development. Inhibitor of apoptosis proteins (IAPs) is a family of intracellular anti-apoptosic proteins. X-linked IAP (XIAP) has been shown to be involved in multiple biological activities (e.g. inhibition of caspase activities, promotion of ubiquitin-proteasome-mediated protein degradation, regulation of cell signaling pathways). The present thesis research project examines: (1) the role and gonadotropic regulation of XIAP expression in rat granulosa cells during ovarian follicular development and atresia; (2) the possible involvement of intra-ovarian factors such as transforming growth factor alpha (TGFalpha) in the FSH-induced XIAP expression and follicular development; and (3) the signal pathways involved in the gonadotropic up-regulation of XIAP during follicular development in vitro.
A follicle culture system coupled to an adenoviral gene manipulation procedure has been established. FSH significantly increased follicular growth as evident by increases in follicular size, cell number and DNA contents in vitro. While cultured pre-antral or early-antral follicles showed a low XIAP content and evidence of apoptosis in the absence of FSH, gonadotropin addition increased XIAP content and suppressed apoptosis. At low FSH concentration, adenoviral XIAP sense cDNA expression increased follicular cell XIAP and DNA contents, reduced apoptosis, and enhanced follicular growth, while XIAP antisense elicited opposite responses. FSH-induced XIAP up-regulation appeared mediated, in part, by the secretion and action of follicular TGFalpha. In cultured rat follicles, FSH-stimulated estradiol production, TGFalpha secretion, XIAP expression and follicular growth were suppressed by intra-follicular injection of a neutralizing anti-TGFalpha antibody or addition of the estradiol antagonist ICI 182780 to the culture media. These results support my hypothesis that the FSH induces follicular growth by stimulating granulosa cell proliferation via theca TGFalpha secretion and action in response to increased granulosa cell estradiol synthesis.
Since the promoter region of XIAP gene has nuclear kappa B (NFkappaB) binding site, it is possible that the transcription of XIAP is mediated via NFkappaB activation. FSH increased rat granulosa cell XIAP mRNA abundance and protein content. While the gonadotropin induced granulosa cell NFkappaB translocation from cytoplasm to nucleus and increased NFkappaB-DNA binding activity, pretreatment with an NFkappaB translocation inhibitor suppressed FSH-stimulated XIAP expression. (Abstract shortened by UMI.)
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Stubbs, Sharon Anne. "The role of insulin-like growth factors and anti-Müllerian hormone in early follicle development in normal and polycystic ovaries." Thesis, Imperial College London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506799.
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Polycystic ovary syndrome (peOS) is the most common cause of anovulation in women of reproductive age. It has recently been shown that as well as abnormalities in the later stages of follicle development, there are also differences in development at the early preantral stages of follicle growth in polycystic ovaries. Specifically, aberrant preantral follicle development in polycystic ovaries is characterised by an increase in the proportion of growing follicles (and a reciprocal decrease in the proportion of primordial, resting follicles) compared to normal ovaries. Our hypothesis is that such abnormalities are due to either an increase in the production (or action) of insulin-like growth factors I or n, or a decrease in the production or action of the inhibitory growth factor AMH. Studies in experimental animals have shown that IGF-I is able to stimulate early folliculogenesis, and preliminary studies in primate pre antral follicles suggest that it may have a similar role in the human ovary. AMH-null mice have been shown to have an increased proportion of growing follicles and a reciprocally reduced proportion of primordial follicles. This phenotype is remarkably similar to that observed in tissue from human polycystic ovaries. The expression of members of the IGF family and TGF-~ superfamily have been studied using immunohistochemistry on formalin fixed, archived human ovarian tissue from normal and polycystic ovaries, and the effect of IGF-I on the initiation of follicle growth is investigated using cultures of human ovarian cortex. The type-l IGF receptor was identified at all stages of follicle development. IGF-I, at a dose as low as lng/ml, was shown to increase the proportion of growing follicles, an effect that was attenuated by adding an antibody to the type-l receptor. AMH immunostaining was examined in normal and polycystic ovaries and the most important finding was that a reduced proportion of follicles stained positively for AMH at the primordial and transitional stages in anovulatory polycystic ovaries. These data support the hypotheses that increased activity of IGFs and reduced expression of AMH (or both), have an important role in aberrant early preantral follicle development in the polycystic ovary.
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Afework, Senait. "Patterns of x-B-Y- catenin E-, P-cadherin, WNTs, frizzled receptors as well as midkine in hair follicle development and growth." Thesis, Queen Mary, University of London, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511377.
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Doyle, Lynsey Kerr. "Role of vascular endothelial growth factor (VEGF) in granulosa cell function : involvement of heterotrimeric G-protein signalling pathways." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4297.
Full textAbstract:
Vascular Endothelial Growth Factor (VEGF) has been shown to be an absolute requirement for ovarian follicle development. Although VEGF is commonly regarded primarily as an angiogenic factor, granulosa cells are a major site of VEGF synthesis in the follicle and they express VEGF receptors (VEGFR1 and VEGFR2). Further, the development of the dominant follicle is characterised by a substantial increase in granulosa cell expression of VEGF and its receptors. In spite of this, potential non-angiogenic effects of VEGF in these follicles have not been elucidated. The objective of the three studies described in this thesis was to use an in vitro bovine granulosa cell model to investigate the roles of VEGF during development of the dominant follicle. In addition, in light of evidence in other cell types, potential interactions between VEGF signalling and heterotrimeric protein signalling in these follicles were also investigated. In the first study, granulosa cells were obtained from healthy follicles with diameters of 4 to 8 mm (corresponding to just before the selection of a dominant follicle during a follicular wave) or 9 to 14 mm (encompassing all developmental stages of a dominant follicle) and exposed to a range of VEGF concentrations (1 to 100 ng/ml) encompassing concentrations found naturally in bovine dominant follicles. VEGF at 1 ng/ml, but not at higher concentrations (P > 0.1), induced significant proliferation of bovine granulosa cells from 4 to 8 mm follicles (P = 0.024) and increased the proliferative response of these cells to FSH (P = 0.045). VEGF also induced a dose-dependent increase in ERK1/2 activation by granulosa cells from 4 to 8 mm follicles (P < 0.03) but did not have any effect on expression of the steroidogenic enzyme, CYP11A1, by these cells (P > 0.1). VEGF, at a dose of 1 ng/ml (P = 0.003), but not at higher doses (P > 0.1), induced an increase in COX-2 expression by granulosa cells from 9 to 14 mm follicles. In addition, LH stimulation of both ERK phosphorylation (P < 0.05) and COX-2 expression (P < 0.05) in granulosa cells from 9 to 14 mm follicles were prevented (P > 0.1) by specific inhibition of VEGFR2, indicating that VEGF may mediate COX-2 responses to LH in these cells. The second study sought to examine the expression of heterotrimeric G-protein á subunits and PLCâ isoforms by real-time PCR and westen blotting in bovine granulosa cells throughout follicle development to identify specific molecular components of heterotrimeric G-protein pathways that may functionally interact with intracellular VEGF signals. Results showed that GNAS, GNA11 and GNAI2 were all expressed at significantly (P < 0.05) higher levels in granulosa cells of pre-ovulatorysize follicles (10.0 to 13.9 mm) than in cells from smaller follicles (2.0 to 5.9 mm and 6.0 to 9.9 mm). In addition, all PLCB isoforms except PLCB2 were expressed in bovine granulosa cells with PLCB3 being more abundant than PLCB1 and -4. Levels of PLCB3 in granulosa cells from pre-ovulatory-size follicles were much higher (>16-fold; P < 0.005) than in smaller follicles. Immunocytochemical analysis revealed that PLCB3 was located primarily in the cytoplasm, whereas PLCB1 was distributed primarily in the nucleus. These results identified Gs, Gq/11, Gi2 and PLCâ3 as candidates for cross-talk between VEGF and heterotrimeric G-protein signalling during the development of the dominant follicle. The potential involvement of these molecules on VEGF-induced responses in granulosa cells from 9-14 mm follicles was investigated in the third study by determining the effects of specific inhibitors of Gi (pertussis toxin, PTX) or Gq/11 (YM-25489) or PLCB3 siRNAs on VEGF-induced p-ERK. Results showed a 2.3 fold mean increase in p-ERK in response to VEGF in the absence of G protein inhibitors (P < 0.0001) but a VEGF response that was completely or partially abolished, respectively, in the presence of PTX (P > 0.8) or YM-25489 (1.6-fold mean increase relative to untreated controls; P = 0.039). LH induced a 1.6 fold increase in p-ERK1/2 (P < 0.02) and this response was prevented by pre-incubation with PTX (P > 0.4) or YM-25489 (P > 0.5). In contrast, similar EGF-induced phosphorylation of ERK (about 5-fold relative to controls) occurred in the absence (P < 0.003) or presence of PTX (P < 0.003) or YM-25489 (P < 0.003). Transfection of granulosa cells with 3 siRNAs targeting PLCB3 that had been previously validated by western blotting and immunocytochemistry had no effect (P = > 0.7) on phosphorylation of ERK in response to VEGF, LH or EGF in granulosa cells. In conclusion, taken together, these results suggest novel roles of VEGF in stimulating granulosa cell proliferation and expression of COX-2 in bovine dominant follicles and implicate VEGF in synergising and/or mediating the effects of gonadotrophins in these cells. In addition, these results indicate a requirement for Gi2 and Gq/11 in VEGF activation of ERK1/2 and induction of the above responses in granulosa cells.
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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.
Full textAbstract:
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.