Molecular Markers of Oocyte Quality and Competence

描述(申请人提供)：这项申请专注于建立具有充分发展潜力的高质量哺乳动物卵母细胞和胚胎的可识别标记。我们的假设是，高质量的卵母细胞是健康后代发育的重要起点，低质量的卵母细胞会导致不孕不育、胚胎和胎儿发育异常，并可能导致后代长期患有成人疾病和障碍。申请者在卵母细胞和卵泡生长发育、卵母细胞、胚胎干细胞和胚胎操作方面有着悠久的、杰出的高质量研究历史；包括编程、重编程、试管受精和胚胎操作以及培养和冷冻保存、胎盘形成和巴克假说(成人疾病的胎儿起源)的研究。我们可以使用茂物的Maccine灵长类动物设施和莫纳什大学的新的国家非人类灵长类动物设施，再加上我们与世界领先的创新试管受精诊所Monash IVF的合作，这意味着我们使用独特动物模型的进步将迅速应用于临床领域。这项应用的目标是发现可测量或可识别的特征，可用于评估正常和异常的人类卵母细胞和胚胎的质量。这将通过增加我们对正常和操纵的哺乳动物卵母细胞的遗传学、表观遗传学、细胞和分子生物学以及蛋白质组学的理解来实现。将健康受者在异种移植前后暴露于母体生活方式疾病(糖尿病和肥胖症)和衰老的卵巢与我们在体外和体内动物模型中为正常卵母细胞和胚胎建立的标准进行比较。我们获得糖尿病、肥胖症和衰老的灵长类动物模型来补充我们的小鼠研究是这一应用的一个重要特征。我们将建立与卵母细胞恢复和完成减数分裂、受精并随后发育成可存活胚胎的能力相关的蛋白质和基因表达谱，无论是在正常发育期间还是对人工刺激的反应。这将为改善体外成熟(IVM)和体外受精(IVF)周期的结果提供机会。这项研究的最终受益者将是那些由于卵子质量低而难以获得健康怀孕和健康后代的妇女。

DESCRIPTION (provided by applicant): This application focuses on establishing identifiable markers of high quality mammalian oocytes and embryos that have full developmental potential. Our hypothesis is that a high quality oocyte is an important starting point for the development of healthy offspring, and that low oocyte quality can lead to infertility, abnormal embryonic and fetal development and possibly long-term adult diseases and disorders in the offspring. The applicants have a long, distinguished, history of quality research into oocyte and follicular growth and development, oocyte, embryonic stem cell and embryo manipulation; including programming, reprogramming, IVF and embryo manipulation and culture and cryopreservation, placentation and the study of the Barker Hypothesis (the fetal origins of adult diseases). Our access to the Maccine Primate Facility at Bogor and the new National Non Human Primate Facility at Monash University, together with our association with a world leading innovative IVF clinic, Monash IVF, means that our advances using unique animal models will be rapidly applied to the clinical arena. This application's goal is to discover measurable or identifiable characteristics that can be used to evaluate the quality of normal and abnormal human oocytes and embryos. This will be achieved by increasing our understanding of the genetics, epigenetics, cell and molecular biology and proteomics of normal and manipulated mammalian oocytes. Ovaries containing oocytes that have been exposed to maternal lifestyle diseases (diabetes and obesity) and ageing before and after xenotransplantation to healthy recipients will be compared to the criteria that we will establish for normal oocytes and embryos in studies undertaken in both in vitro and in vivo animal models. Our access to primate models of diabetes, obesity and ageing to complement our murine studies are a significant feature of this application. We will establish protein and gene expression profiles correlated with the ability of an oocyte to resume and complete meiosis, fertilise and subsequently develop into a viable embryo, both during normal development and in response to artificial stimulation. This should provide the opportunity to improve outcomes for both in vitro maturation (IVM) and in vitro fertilisation (IVF) cycles. The ultimate beneficiaries of this research will be women who have difficulty attaining healthy pregnancies and healthy offspring because of low egg quality.