Résumé : L’adénocarcinome colorectal est parmi les plus importants cancers au Canada en terme de mortalité et morbidité. Cependant, nous n’en connaissons encore que peu, entres autres sur les voies cellulaires importantes et les protéines présentant un potentiel comme biomarqueur. Cette étude fut divisée en deux sous-projets. Sous-projet A. Il n’y a présentement aucun biomarqueur permettant de prédire la réponse à la radiothérapie comme modalité de traitement pour le cancer colorectal. Le but de ce sous-projet était de mettre au point les méthodes permettant d’effectuer une étude prospective ou rétrospective par spectrométrie de masse sur la réponse à la radiothérapie en utilisant des échantillons de tissu de patient. Des échantillons de tissu de souris et de tissu humains anonymisés ont été utilisés pour évaluer la faisabilité d’une telle étude. Différentes techniques d’extraction protéique ont été évaluées. Les extraits totaux et fractionnements subcellulaires de tissu frais ont permis une analyse appropriée des protéines cellulaires. Il en était de même pour l’extraction totale de tissus fixés. Cependant, les protéines extraites suite à microdissection au laser de tissu fixé étaient inadéquates et en nombre insuffisant. Sous-projet B. Afin d’investiguer l’importance de fonctions, voies ou protéines dans différents types de cancer colorectaux, neuf lignées cellulaires de cancer colorectal et de côlon normal ont été fractionnées en quatre compartiments subcellulaires et analysées par spectrométrie de masse. Aucun groupe de recherche n’avait analysé jusqu’à présent plus de cinq lignées et plus d’un compartiment subcellulaire à la fois. Les résultats montraient que certaines voies canoniques et fonctions cellulaires étaient de haute importance dans plusieurs des lignées analysées, dont la voie de signalisation par eIF2. De plus, les régulateurs de transcription TP53, MYC et TGFB1, pouvant être responsables des caractéristiques cellulaires observées, ont été identifiés. En conclusion, ce projet nous a permis d’améliorer nos connaissances sur les caractéristiques moléculaires d’importance dans le cancer colorectal et de mettre au point des techniques qui pourraient permettre la découverte de nouveaux biomarqueurs. / Abstract : Colorectal adenocarcinoma is one of the most important cancers in Canada in terms of mortality and morbidity. However, we still know very little on its molecular features. This study was divided into two sub-projects. Sub-project A. At this time, no biomarker has the capacity of predicting a patient’s response to radiotherapy, which is a commonly used treatment of colorectal cancer. The goal of this section was to develop the methods to conduct a prospective or retrospective mass spectrometry study on the patient response to radiotherapy, through the use of human tissues. Mouse tissues and tissues of an anonymous patient were obtained in order to evaluate the feasibility of such a study. Different protein extraction techniques were evaluated. Total lysates and subcellular fractionations of fresh tissues allowed for a successful analysis of the samples. The same was true of total lysates of fixed tissues. However, proteins extracted from cells isolated through laser capture microdissection were insufficient in numbers and their types were inconsistent with the expected results. Sub-project B. In order to study the importance of proteins and cellular functions or pathways in different types of colorectal cancers. nine cell lines originating from colorectal carcinoma and from normal colon were fractionated according to four subcellular compartments and analysed through mass spectrometry. Until now, no research group had analysed, in a single study more than 5 cell lines as well as more than one subcellular compartment at once. Some cellular functions and canonical pathways were shown to be of high importance in many of the studied cell lines, such as the signalling through eIF2 pathway. Furthermore, the transcription regulators TP53, MYC and TGFB1were identified as potentially responsible for the observed proteomic characteristics. In conclusion, this study allowed for a better understanding of important molecular caracteristics of colorectal cancer and allowed for the optimization of techniques that may serve in the discovery of new biomarkers relative to the use of radiotherapy as a treatment.

Magister Artium - MA / The concern that weather variability and climate change has raised nowadays puts every society or community on the alert. This is arguably the most persistent environmental threat to global stability in vulnerable communities in recent times. City dwellers are now experiencing increased variable weather episodes such as frequent flooding, heat waves and drought with increased wind and storm activities. Unfortunately, the aftermath of these weather irregularities are felt most severely by vulnerable urban poor residents with the least mechanisms to cope. This study focused on the residents of Enkanini in Makhaza, an informal settlement in the greater Khayelitsha Township of Cape Town, South Africa. It documented the challenges they encounter with respect to weather, seeking to understand their adaptive strategies. Emphasis was also placed on the vulnerable nature of their dwellings and their ingenuity in coping with the variable weather pattern in Cape Town. Qualitative and quantitative methods were used to analyse field data, using codes derived from themes and SPSS respectively. Ethnographic methodology guided the researcher to participate overtly in the activities of the community over an extended period, watching what happened, listening to what was said and asking questions pertaining to their vulnerability to the vicissitudes of the prevailing weather in the informal settlement. Findings from the study revealed that over 62% of the dwellings do not conform to the City‟s Disaster Risk Management Centre and Fire & Rescue safety regulations and that over 80% of the residents do not adapt very well to weather-related episodes. It also identifies the most challenging weather episodes to be floods during winter and shack fires during summer; amidst other health concerns that occur all year round.

Cardiovascular disease (CVD) is the leading cause of death worldwide, and is projected to remain so for at least the next decade. Ever since its discovery in the urine and blood of children with inborn errors of metabolism, homocysteine (Hcy) at elevated plasma concentrations has been associated with CVD clinically and epidemiologically. Observational studies and meta-analyses have noted that changes in plasma Hcy by 5μM increase the odds ratio of developing coronary artery disease by 1.6-1.8 among other CVD. Clinical trials aimed at reducing plasma Hcy for benefit against development of subsequent cardiovascular events have had unconvincing results, but have moreover failed to address the mechanisms by which Hcy contributes to CVD. Recommendations from national agencies like the American Heart Association and the United States Preventive Services Task Force emphasize primordial prevention as a way to combat CVD. Reducing plasma Hcy as secondary and primary interventions does not fulfill this recommendation. In order to best understand the role of Hcy in CVD, an investigation into its mechanisms of action must be undertaken before measures of primordial prevention can be devised. Numerous experimental studies in the literature identify vascular endothelium as a target for the pathological effects of Hcy. Endothelial injury and impairment are contributory processes to atherosclerosis, and Hcy has been demonstrated to inhibit endothelial cell (EC) growth and proliferation through mechanisms involving cell cycle arrest, oxidative stress, and programmed cell death in vitro. Animal models have also confirmed that high levels of Hcy accelerate atherosclerotic plaque development and lead to impairment of vascular reendothelialization following injury. Hcy has been shown to have the opposite effect in vascular smooth muscle cells (SMC), causing their proliferation and again contributing to atherosclerosis. The cell-type specificity of Hcy remains to be understood, and among the aims of this research was to further characterize the effects of Hcy in EC. The overarching goal was discovery in order to direct future investigations of Hcy-mediated pathology. To begin, the first investigation considered the transcriptional and regulatory milieu in EC following exposure to Hcy. High-throughput screening using microarrays determined the effect of Hcy on 26,890 mRNA and 1,801 miRNA. Two different in vitro models of hyperhomocysteinemia (HHcy) were considered in this analysis. The first used a high dose of 500µ Hcy to mimic plasma concentrations of patients wherein the transsulfuration pathway of Hcy metabolism is impaired as in inborn cystathionine-ß-synthase deficiency. The other set of conditions used 50µ Hcy in the presence of adenosine to approximate impairment of the remethylation pathway of Hcy metabolism wherein s-adenosylhomocysteine accumulates, thus inhibiting s-adenosylmethionine formation and methylation reactions. These distinctions are important because most clinical trials do not distinguish between causes of HHcy, thereby ignoring the specific derangements underlying HHcy. mRNA and miRNA expression changes for both sets of treatment conditions identified CVD as a common network of Hcy-mediated pathology in EC. Moreover, methylation-specific conditions identified cell cycle modulation as a major contributory mechanism for this pathology, which agrees with recent findings in the literature. Analysis of significant mRNA changes and significant miRNA changes independently identified roles for Hcy in CVD and cell cycle regulation, thereby suggesting that miRNA may mediate the effects of Hcy in addition to gene expression changes alone. To investigate the role of Hcy in the cell cycle further, the next set of investigations considered the effect of Hcy under conditions approximating impaired remethylation in early cell cycle events. Previous studies have demonstrated that Hcy inhibits cyclin A transcription in EC via demethylation of its promoter. Conversely, Hcy induces cyclin A expression in SMC, again making the case for a cell type-specific mechanism in EC. Preceding cyclin A transcription and activation, canonical events in the early cell cycle include D-type cyclin activation, retinoblastoma protein (pRB) phosphorylation, and transcription factor E2F1 activation. In a series of in vitro experiments on EC, it was seen that Hcy inhibits expression of cyclin D2 and cyclin D3, but not cyclin D1. Next, pRB phosphorylation was seen to be decreased following treatment with Hcy. This also led to decreased E2F1 expression. However, this series of events could be reversed with E2F1 supplementation, allowing the cell cycle to proceed. As Hcy exerts a number of its effects via regulation of gene transcription, a final series of investigations aimed to predict potential targets of Hcy by examining patterns of transcription factor binding among known targets of Hcy regulation. Gene promoters of Hcy-modulated genes were analyzed in order to determine common transcription factors that potentially control their regulation. The locations of CpG-rich regions in promoters were identified to determine which regions would be most susceptible to regulation by DNA methylation. Next, high-throughput next-generation sequencing (NGS) and bisulfite NGS was performed for DNA from EC treated with Hcy in order to determine methylation changes after Hcy treatment. A number of potential transcription factors and their binding sites were identified as potential mediators of Hcy-mediated gene regulation. Taken together, these investigations represent an exploration of Hcy-mediated pathology in CVD, by focusing upon novel regulatory mechanisms in EC. Objective high-throughput arrays identified roles for Hcy in CVD and cell cycle pathways regulated by miRNA and gene expression, which were confirmed experimentally in vitro. These observations led to an investigation and identification of common transcription factors that potentially regulate Hcy-altered gene expression. This framework may be used to guide future investigations into the complex pathological network mediating the effects of Hcy in CVD. First, identification of a role for miRNA in mediating the effects of Hcy represents a novel regulatory mechanism, heretofore largely unexplored. Next, expanding the role of Hcy in EC cell cycle regulation to identify upstream mediators greatly adds to the published literature. Finally, noting that these changes center upon transcriptional and post-transcriptional regulation gives import to developing methods to characterize promoter and transcription factor regulation. The investigations presented herein and their results provide evidence that the future of Hcy research is vibrant, relevant, and not nearly surfeit. / Pharmacology

In early criticism of Western Canadian literature, prairie spaces were constructed as predominantly rural in order to set the region and prairie writing apart from the rest of Canada and other Canadian literature. In time, prairie criticism’s focus on rural realist texts led to the marginalization of urban prairie writing and the construction of urban spaces as corrupt and artificial in comparison to the natural and virtuous rural environment. I work to remedy the absence of urban texts in the criticism of prairie literature, and I argue that prairie cities are dynamic and mobile worlds where prairie inhabitants exercise their agency through everyday practices. Utilizing the work of Raymond Williams, I show how urban and rural spaces are constructed in the canonical prairie texts of Grove, Ostenso, and Stead to serve various capitalist interests and colonial ideologies. I explore the depiction of Winnipeg in Durkin’s The Magpie as a dynamic, complex, and politically engaged space. Moreover, I use Michel de Certeau’s work to assert that the underprivileged and colonized individuals in the city subvert and utilize the systems and organizations of those in power. They develop an increased deviousness and take advantage of incidental and multifarious opportunities that come their way as they work, dwell, and move about in everyday life. Subsequently, I look at urban writing by women, Eastern-European immigrants, and Aboriginal writers and show that they use urban spaces, everyday practices, and writing to exercise their agency. To destabilize unitary forces in language, to depict their own experiences, and to convey their own meanings of home, labour, and community, marginalized writers employ wordplay, humour, historical and cultural references, and intertextuality. I also use Jane M. Jacobs’ work on postcolonial cities and Tim Cresswell’s theories of mobility. I read prairie cities as places of competing mobilities and networks of dominances and resistances, where colonized individuals negotiate complex, hybrid, and authentic identities. The urban prairie texts I explore demonstrate the possibility of political, social, and economic changes, and a beneficial relationship with the prairie environment.

L’objet de cette thèse est de rendre compte des spécificités d’un genre poétique ingénieux, l’énigme, devenu caduc et qui a longtemps été dédaigné par la critique littéraire en raison de sa dimension ludique. Elle n’en a pas moins connu une ample carrière tout au long de la première modernité, comme en attestent de nombreux manuscrits et séries éditoriales. Nous abordons cette forme procédant du genre de discours de la devinette, dont l’étude a longtemps été réservée à l’anthropologie, du point de vue de l’histoire littéraire et de l’histoire des formes. Cette thèse expose les nombreuses filiations littéraires de l’énigme en langue française ainsi que ses enjeux pragmatiques dans le contexte des salons, où elle est adaptée aux règles du jeu de la conversation et de la civilité mondaine. L’analyse poétique et rhétorique démontre que, loin d’être une forme hermétique, l’énigme subordonne l’effet obscur de la parole poétique à l’éclat ingénieux. Genre à contrainte et genre sériel, elle constitue un laboratoire de la création poétique de l’Ancien régime, donnant lieu à de nombreuses inventions facétieuses et galantes. L’étude des collections d’énigmes publiées entre les années 1570 et 1720 rend compte, au-delà de la répétition des thèmes et des formes, de possibilités d’énonciation originale des « mystères ingénieux ». Elle révèle aussi le rôle central de l’allusion dans l’invention du discours littéraire de la première modernité. / The purpose of this work is to present the characteristics of an ingenious poetic genre, the enigma, which is nowadays considered obsolete and has long been underestimated by critics on account of its recreational dimension. However, the early modern times have made an extensive use of it, as many manuscripts and print series show. We tackle this form, linked to the riddle genre, which study has long been the field of anthropology, from the perspective of the history of literature and of the history of literary form. We highlight the numerous literary sources of the French enigma, as well as the practical questions at stake in the framework of high society salons that adapted it according to the rules of conversation and politeness. The poetical and rhetorical analysis shows that, far from being an arcane form, the enigma uses obscurity in order to create an ingenious brightness. Despite being strictly rule-bound and serial, the genre makes space for a huge diversity of poetical creation and provides facetious and gallant inventions. Studying the collections of enigmas published between 1570 and 1720 shows that, beyond the repetitive themes and forms, it is still possible to think up genuine “ingenious mysteries”. It also reveals the fundamental part played by allusion in the invention of a literary discourse in the early modern times.

Nombreux sont les travaux consacrés aux Essais à avoir embrassé d’un seul regard les caractéristiques littéraires et la teneur philosophique du livre de Montaigne. Mais la nature philosophique de la prose d’idées des Essais restait une évidence inquestionnée ; c’est ainsi que s’est constituée une représentation opaque de l’œuvre selon laquelle l’ensemble réputé inextricable de ses aspects ne pouvait être pensé qu’à travers la catégorie doxographique du scepticisme. Enquête méthodologique et critique, la présente thèse vise à dissiper cette opacité en dégageant spéculativement les fondements d’une manière alternative de rendre compte de la philosophie dans les Essais à partir de son articulation avec les propriétés du texte. L’expérience que le lecteur des Essais peut faire de la philosophie montanienne est spécifique : cette philosophie se manifeste comme détermination. Est ensuite démontrée la nécessité méthodologique de localiser la philosophie à sa juste échelle dans le texte pour pouvoir rigoureusement l’identifier. Il apparaît alors que ce n’est qu’à la faveur d’une compréhension poïétique des ressorts textuels de la pensée montanienne que devient véritablement pensable la philosophie des Essais. La description de la philosophie des Essais sur laquelle débouche cette investigation permet enfin de prendre la pleine mesure de l’inventivité d’une pensée tributaire d’une écriture, aux sens matériel et stylistique du terme. / It is common practice for works pertaining to Montaigne's Essays to embrace in a single glance its literary characteristics and its philosophical content. But the philosophical nature of the Essays' non-fictional prose has yet remained unchallenged, crystallizing an opaque representation of the text that precludes its supposedly inextricable aspects from being thought outside the doxographic category of skepticism. A methodological and critical enquiry, the present thesis intends to dispel this opacity by speculatively unfolding the fundamental principles for an alternative construal of the Essays' philosophical content, rooted in its articulation with the properties of the text. The way in which the reader of the Essays shall experience Montaigne's philosophy is specific: this philosophy emerges as semantically determined content. From this ensues the methodological imperative to localize philosophy at its legitimate scope of focus within the text in order to allow for its rigorous identification. It then appears that philosophy of the Essays can only be truly thought through the lens of a poietic understanding of the textual elements of Montaigne’s thought. Finally, the description of the philosophy of the Essays brought about by this enquiry sheds light on the full extent of the ingenuity of Montaigne's thought, tributary of his writing in both the material and stylistic senses of the term.

Little is known about the signaling pathways that contribute to treatment response in advanced stage head and neck tumors. Increased expression of epidermal growth factor receptor (EGFR) and downstream pathways such as nuclear factor kappa B (NFκB) are implicated in aggressive tumor phenotypes and limited response to therapy. This study explored the rationale for combining the proteasome inhibitor bortezomib with the EGFR inhibitor gefitinib in a subset of head and neck squamous cell carcinomas with high EGFR gene amplification. Drug responses of gefitinib and bortezomib as single agents and in combination within head and neck squamous cell carcinoma cell lines were analyzed using MTS assays. The effects of gefitinib on the activation of EGFR and itsthree major downstream pathways, Akt, STAT3 and MAPK were determined by western blotting. The activation status of NFκB and the effects of bortezomib on the canonical pathway were assessed by DNA binding assays. Resistance to lower doses of gefitinib was associated with elevated EGFR and activated Akt expression. Gefitinib was able to effectively inhibit activation of STAT3, Akt and MAPK in HNSCC to varying degrees depending on EGFR expression status. Bortezomib treatment inhibited TNFα –induced nuclear NFκB/RelA expression but demonstrated variability in levels of baseline nuclear NFκB/RelA expression between sensitive and resistant cell lines. Bortezomib effectively suppresses NFκB/RelA nuclear activation but demonstrates additional modes of cellular toxicity beyond the NFκB pathway in sensitive cell lines. Further understanding of tumor response to the targeted inhibitors gefitinib and bortezomib may provide novel approaches in managing HNSCCs.

Building on recent scholarship in the history of art which has started to reappraise the meaning of grotesque and scatological motifs, this thesis examines how digestion was conceived of as a model of creation, and how this was translated visually. Renaissance creativity was increasingly modelled on a series of natural processes like digestion, following a trend in favour of Aristotelian psychology. However, it has been largely overlooked in comparison to the bleeding, the pneumatic, and especially the procreative natural models, which have been extensively studied. The central argument of this thesis is that digestion constituted an alternative-albeit less 'decorous'-model of creation, denoting the intervention of a more 'earthbound' ingenium. I argue that this model was used by certain classes of artists as an acknowledgement of a strong engagement with materials and of the labour of a round-the-clock imagination. Goldsmithing and printmaking are artistic professions whereby the artistic process was often considered as an act of 'soiling' oneself, both in the sense of the body and the phantasia. This thesis focuses on a period spanning c. 1530 to 1675, from Rabelais' works to the facetious printer Jacques Lagniet. It mines a corpus of little-studied textual and visual sources from the north of the Alps, examining a continuity between France and the German lands: geographical areas which both had an especially pronounced 'culture of excretion'. From a broader perspective, this research responds to a widespread scholarly call for more attention to the organic soul and the lower body, nuancing the alleged hegemony of the brain and the higher senses throughout history. It seeks to modify the perception of early modern artists and viewers as cerebral intellectuals, presenting them as individuals who also 'thought with their guts'.

In recent years, urban historians have established that the period from 1560 to 1660 was a key era for London’s development from a relatively small European urban centre into a large dynamic global capital. This dissertation attempts to intervene in London scholarship by drawing attention to the economic, political, religious and – most significantly – cultural importance of clothing in the city in this period. Using material, visual, literary and archival sources, it explores the ways clothing contributed to the development of early modern London and, in turn, how London’s rapid growth changed the making, wearing, and meaning of clothing. This dissertation places material evidence at the fore using extant objects from museum collections. It also employs the new methodology of reconstruction to explore craft, ingenuity, and emotional self-expression in dress. As clothing infused economic and social life, it draws upon on a wide range of evidence, from London guild records, to portraits, travel accounts, personal letters, diaries and account books, plays, sermons and poems. With a focus on urban experience, this dissertation discusses not only elite luxury consumption, but also investigates the wardrobes of guildsmen, immigrant craftspeople, apprentices and maids – asking what they wore, what they thought about what they were wearing, and how they used clothing to navigate through the city during this time of rapid change. A chapter on the ‘London Look’ shows how inhabitants and visitors documented the visual and material styles of the city. Exploring the collaborative processes by which clothing was made, worn and appreciated by craftspeople and consumers, a chapter on making and buying clothing demonstrates how clothes were made and charts the emergence of a new consumer culture. Existing scholarship on sumptuary laws is challenged in a chapter that demonstrates how laws were enforced in the city while also integrating extant objects into the discussion for the first time. Finally, using a sample of London wills, the dissertation shows how Londoners owned, bequeathed and inherited clothing, and imbued it with emotional meaning. In sum, this dissertation aims to integrate scholarship on early modern London with material culture studies, and to promote the new methodology of reconstruction for historians. In revealing how London was conceived during a time of rapid change, clothing can be used as a lens through which to explore wider discourse about a city that by 1657 was being described as ‘Londinopolis.’ Clothing helped to make London into a wealthy, dynamic, and diverse urban centre, and these changes dramatically shaped the way clothing was made and appreciated.

Advanced maternal age has been shown to influence follicular and luteal dynamics in bovine ovary resulting in reduced fertility. The overall objective of the four studies presented in this thesis is to identify the maternal age-associated transcriptional changes in granulosa cells of the dominant follicles during follicle development. In the first study, mRNA expression levels of housekeeping genes were measured by real–time quantitative PCR (RT-qPCR) in granulosa cells of dominant follicles and FSH-stimulated follicles to select and validate suitable reference genes for relative gene expression analyses during maternal and follicular aging. Stability of six reference genes (GAPDH, ACTB, EIF2B2, UBE2D2, SF3A1 and RNF20) was analyzed using GeNorm, DeltaCT and NormFinder programs and comprehensive ranking order was determined based on these programs. Geometric mean of multiple genes (UBE2D2, EIF2B2, GAPDH and SF3A1) was more appropriate reference control than individual genes for the comparison of relative gene expression among dominant and FSH-stimulated follicles during maternal and/or follicular aging studies. In the second study, maternal age-associated changes in the transcriptome of granulosa cells recovered at the time of selection of the dominant follicle from aged (n=3) and young cows (n=3) were determined by EmbryoGENE bovine oligo-microarrays (EMBV3, Agilent Technology). The mRNA expression of five transcripts (CYP19A1, PCNA, GJA1, TPM2, and VNN1) was confirmed in a different set of granulosa cell samples by RT-qPCR to validate microarray data. A total of 169 genes/isoforms were differentially expressed (≥ 2-fold-change; P ≤ 0.05) in aged cows vs. young cows. These transcripts revealed inefficient 1) control of gonadotropins, and gonadotropin-induced changes in the cytoskeleton and extracellular matrix, 2) lipid metabolism and steroidogenesis 3) cell proliferation, cell cycle control and intercellular communication, and 4) higher oxidative stress responses in aged cows vs. young cows. In the third study, changes in the transcriptome of granulosa cells of the preovulatory follicle 24 h after LH treatment from aged (n= 3) and young (n=3) were determined. A total of 1340 genes were expressed differentially (≥ 2-fold change; P ≤ 0.05) in aged cows vs. young cows. The mRNA expression of five transcripts (RGS2, PTGS2, TNFAIP6, VNN1, NR5A2 and GADD45B) was confirmed in a different set of granulosa cell samples to validate microarray data. These transcripts were related to delayed 1) response to LH treatment 2) cellular differentiation and luteinization and 3) progesterone synthesis. Intra-follicle levels of progesterone were lower (P < 0.05) in aged cows compared to young and mid-aged cows. The fourth study compared the aged-associated changes in the transcriptome of granulosa cells during follicle development from the time of dominant follicle selection to preovulatory stage (24 h after LH). In comparison to young cows, aged cows expressed fewer differentially expressed genes/isoforms (1206 vs. 2260, respectively) at ≥ 2-fold-change (P ≤ 0.05) in the granulosa cells of the preovulatory (24 h after LH treatment) vs. the dominant follicle at selection. These transcripts in aged cows were related to late and inefficient 1) organization of cytoskeleton and cytoplasm, 2) differentiation, 3) lipid and cholesterol metabolism, 4) proliferation and 5) higher response to oxidative stress and free radical scavenging in the preovulatory follicles vs. the dominant follicle at selection. In conclusion, maternal age-alters the gene expression of granulosa cells of the dominant follicles during follicle development and results in a compromised follicular environment.