regulation of bovine endometrial function during the estrous cycle and early pregnacy

发情周期和妊娠早期牛子宫内膜功能的调节

• 批准号: 8161-2007
• 负责人: Goff, Alan
• 金额: $ 2.63万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2008
• 资助国家: 加拿大
• 起止时间: 2008-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=389676
• 关键词: regulation; bovine; endometrial; function; during

The ovarian hormones estradiol (E2) and progesterone (P4) control the ordered growth and differentiation of uterine cells. This remodeling process, which is modified by signals from the developing embryo, is critical for implantation, the formation of the placenta, and maintenance of pregnancy. Failure of uterine tissues to respond appropriately to ovarian hormones or the embryo results in defective placentation, associated with a spectrum of pregnancy disorders. These disorders are a major cause of maternal and perinatal morbidity and mortality. As well as their effects on the structure of the endometrium, P4, E2 & the embryo also regulate its function; for example, prostaglandin synthesis and the oxytocin receptor (OTR) during luteolysis and parturition. In vivo, the P4 produced during the luteal phase down regulates the OTR and prevents luteolysis from occurring too soon. However, the mechanisms involved in the action of P4 are not understood since downregulation of OTR by P4 in vitro is problematic. The first main objective of the proposed work is to understand the mechanisms of action of P4 in the endometrium of the cow. The interaction between multiple receptors, coactivators, and repressors within the different cell types of the endometrium involved in the regulation of OTR will be elucidated. The second area of research will examine the regulation and the action of two proteins, MIF and soluble E-cadherin, secreted from the endometrial epithelial cells. I have previously shown that secretion of these proteins is stimulated by interferon-tau, the embryonic signal responsible for the maintenance of pregnancy in the cow. It is hypothesized that they play a role in tissue remodeling prior to implantation. The significance of this work is that it will provide important basic information on the action of P4 in the endometrium and on interaction between the embryo and uterus necessary for implantation. In the cattle industry this could lead to ways of improving pregnancy rates, which will be of great economic benefit to Canada. The results of this work could also be relevant to human health and lead to a better understanding of parturition and a decrease in early embryonic loss.

卵巢激素雌二醇（E2）和黄体酮（P4）控制子宫细胞的有序生长和分化。这种重塑过程会受到发育中胚胎信号的影响，对于植入、胎盘形成和妊娠维持至关重要。子宫组织未能对卵巢激素或胚胎做出适当反应，导致胎盘形成缺陷，从而导致一系列妊娠疾病。这些疾病是孕产妇和围产期发病和死亡的主要原因。 除了对子宫内膜结构的影响外，P4、E2 和胚胎还调节其功能；例如，黄体溶解和分娩过程中前列腺素的合成和催产素受体（OTR）。在体内，黄体期产生的 P4 下调 OTR 并防止黄体溶解过早发生。然而，P4 的作用机制尚不清楚，因为 P4 在体外下调 OTR 是有问题的。这项工作的第一个主要目标是了解 P4 在牛子宫内膜中的作用机制。子宫内膜不同细胞类型内参与 OTR 调节的多种受体、共激活因子和阻遏因子之间的相互作用将得到阐明。第二个研究领域将检查子宫内膜上皮细胞分泌的两种蛋白质（MIF 和可溶性 E-钙粘蛋白）的调节和作用。我之前已经证明，这些蛋白质的分泌是由干扰素 tau 刺激的，干扰素 tau 是负责维持奶牛妊娠的胚胎信号。据推测，它们在植入前的组织重塑中发挥作用。这项工作的意义在于它将提供关于 P4 在子宫内膜中的作用以及植入所需的胚胎和子宫之间的相互作用的重要基础信息。在养牛业中，这可能会导致提高怀孕率的方法，这将为加拿大带来巨大的经济效益。这项工作的结果也可能与人类健康相关，并有助于更好地了解分娩和减少早期胚胎丢失。